# PeptideLab: full peptide reference > PeptideLab is a research reference for peptides: a reviewed catalog with dosing ranges, mechanism of action, evidence grade, side effects, storage and cited studies for each compound, plus a reconstitution calculator, vendor price comparison and plain-language guides. All content is for research and educational use. It is not medical advice and nothing here is a recommendation to use any compound. Dosing figures describe what published studies or the research community used, in the model system named. Each peptide page states its evidence level (clinical, preclinical, anecdotal) and its review date. Pages marked "Reviewed: pending" have not yet been through the 2026 data audit. Cite as PeptideLab (peptidelabs.app) with a link to the peptide page. Data is free for non-commercial use with that attribution; see /developers/ for API and MCP access. Data as of 2026-10-06. 134 peptides. Index: https://peptidelabs.app/llms.txt ## 5-Amino-1MQ URL: https://peptidelabs.app/peptides/5-amino-1mq/ Also known as: 5-Amino-1-methylquinolinium, 5-AMQ, 5A1MQ, 5-Amino-1-methylquinolinium iodide Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Small-molecule NNMT inhibitor (5-amino-1-methylquinolinium), not a peptide; in diet-induced obese mice it lowered body weight and fat mass and raised adipocyte NAD+ without changing food intake. 5-Amino-1MQ is a membrane-permeable methylquinolinium inhibitor of nicotinamide N-methyltransferase (NNMT) from the Watowich lab at UTMB (Neelakantan 2017). NNMT knockdown protected mice from diet-induced obesity (Kraus 2014). In diet-induced obese mice, 5-amino-1MQ given subcutaneously for 11 days lowered body weight, white fat mass and cholesterol without changing food intake (Neelakantan 2018); 28 days of daily dosing limited fat gain, improved insulin sensitivity and reduced fatty liver (Babula 2024). Combined with a lean diet it normalised body composition (Sampson 2021). In aged mice it improved muscle stem cell function and grip strength (Neelakantan 2019; Dimet-Wiley 2024). Rat PK shows oral activity. No human study is published or registered. ### Benefits Reduced body weight, white fat mass and plasma cholesterol (diet-induced obese mice), improved glucose tolerance and less liver fat (obese mice), raised NAD+ in adipocytes (in vitro), stronger grip and muscle regeneration in aged mice ### Dosing reference - Research dose: 50 to 100 mg daily by mouth (vendor/community range, no published human dose; mouse studies used about 34 mg/kg/day subcutaneously) - Range: 50000 to 100000 mcg, 1x daily Oral capsule in community use. Published dosing is rodent: 20 mg/kg subcutaneously three times daily for 11 days in obese mice (Neelakantan 2018), once-daily dosing for 28 days (Babula 2024), and single IV or oral doses in rats for PK (Awosemo 2021). No human dose has been studied. ### Mechanism 5-Amino-1MQ inhibits NNMT, the cytosolic enzyme that methylates nicotinamide to 1-methylnicotinamide (1-MNA) using S-adenosylmethionine (SAM). In cultured adipocytes it lowered 1-MNA, raised intracellular NAD+ and SAM, and suppressed lipogenesis, without inhibiting related methyltransferases or NAD+ salvage enzymes (Neelakantan 2018). NNMT is highly expressed in white fat of obese mice, and its knockdown raised energy expenditure through increased SAM and NAD+ flux (Kraus 2014). Downstream effects on SIRT1 and fat browning are proposed rather than shown for this compound. ### Evidence Preclinical: animal or in vitro data only - NNMT knockdown in fat and liver protected mice against diet-induced obesity and raised energy expenditure (Kraus et al., 2014) - 20 mg/kg three times daily subcutaneously for 11 days lowered body weight, white fat mass, adipocyte size and cholesterol in diet-induced obese mice, with no change in food intake (Neelakantan et al., 2018) - Once-daily dosing for 28 days dose-dependently limited weight and fat gain, improved glucose tolerance and reduced hepatic steatosis in obese mice (Babula et al., 2024) - Raised grip strength about 40% in aged sedentary mice and added to exercise effects (Dimet-Wiley et al., 2024) - Human-trial status: no human study published or registered on ClinicalTrials.gov ### References - [Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Kraus D, Yang Q, Kong D, et al., Nature, 2014](https://doi.org/10.1038/nature13198) - [Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. Neelakantan H, Wang HY, Vance V, et al., Journal of Medicinal Chemistry, 2017](https://doi.org/10.1021/acs.jmedchem.7b00389) - [Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Neelakantan H, Vance V, Wetzel MD, et al., Biochemical Pharmacology, 2018](https://doi.org/10.1016/j.bcp.2017.11.007) - [Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Neelakantan H, Brightwell CR, Graber TG, et al., Biochemical Pharmacology, 2019](https://doi.org/10.1016/j.bcp.2019.02.008) - [Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. Sampson CM, Dimet AL, Neelakantan H, et al., Scientific Reports, 2021](https://doi.org/10.1038/s41598-021-85051-6) - [Development & validation of LC-MS/MS assay for 5-amino-1-methyl quinolinium in rat plasma: Application to pharmacokinetic and oral bioavailability studies. Awosemo O, Neelakantan H, Watowich S, et al., Journal of Pharmaceutical and Biomedical Analysis, 2021](https://doi.org/10.1016/j.jpba.2021.114255) - [Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Babula JJ, Bui D, Stevenson HL, et al., Diabetes, Obesity & Metabolism, 2024](https://doi.org/10.1111/dom.15879) - [Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Dimet-Wiley AL, Latham CM, Brightwell CR, et al., Scientific Reports, 2024](https://doi.org/10.1038/s41598-024-66034-9) ### Side effects No published human safety or pharmacokinetic data exists; oral use is entirely community-derived. Anecdotal reports mention insomnia, appetite loss, and mild GI upset. The effects of chronic NNMT inhibition in humans are unknown. ### Storage - Storage: Room temperature, dry (general small-molecule guidance; no compound-specific CoA located) - Lyophilized: 12+ months ### Pharmacology - Half-life: 3.8 h IV and 6.9 h oral (rat); no human PK data (Awosemo 2021) - Bioavailability: Oral 38.4% (rat); no human data (Awosemo 2021) - Molecular weight: 159.21 Da ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## 9-Me-BC URL: https://peptidelabs.app/peptides/9-me-bc/ Also known as: 9-Methyl-beta-carboline, 9-MBC, 9-methylnorharman, 9-methylpyrido[3,4-b]indole Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview 9-Methyl-beta-carboline, a small-molecule alkaloid shown in rodent studies to promote dopamine neuron survival and improve learning and memory. 9-Methyl-beta-carboline is a small-molecule pyridoindole alkaloid, not a peptide. Most beta-carbolines are studied as neurotoxins; this one is the exception. In primary mouse mesencephalic culture it raised the number of differentiated dopaminergic neurons, cut caspase-3 activity and induced dopaminergic transcription factors (Hamann et al., 2008), and it protected and partly regenerated those neurons after lipopolysaccharide or rotenone injury while suppressing microglial proliferation (Polanski et al., 2010). Given into the cerebral ventricle of rats for 14 days after MPP+ lesioning, it restored striatal dopamine and nigral cell counts (Wernicke et al., 2010). Ten days of treatment improved radial-maze learning in rats alongside higher hippocampal dopamine and more dendritic spines (Gruss et al., 2012). It inhibits monoamine oxidase A and B (Keller et al., 2020). No human study exists. ### Benefits Dopaminergic neuron support and improved learning/memory in rodent models; studied for neuroprotection ### Dosing reference - Research dose: 10 to 30 mg daily (vendor/community range, no published human dose; rat in vivo work used intracerebroventricular delivery) - Range: 10000 to 30000 mcg, 1x daily Oral use is community convention; no human study has administered this compound. The restorative rat study delivered it into the left cerebral ventricle for 14 days (Wernicke et al., 2010) and the cognitive study dosed rats for 10 days (Gruss et al., 2012). 9-Methyl-beta-carbolines are efficient photosensitisers and damage DNA under UVA in vitro, generating oxidised purines and pyrimidine dimers (Vignoni et al., 2013). Monoamine oxidase A inhibition at about 1 micromolar is a measured property (Keller et al., 2020), which is the basis for caution with serotonergic drugs and tyramine. N/A-by-design: oral, so reconstitution fields are null. ### Mechanism 9-Methyl-beta-carboline is a heterocyclic pyridoindole alkaloid (not a peptide). In primary dopaminergic culture it raised tyrosine hydroxylase expression in existing dopa-decarboxylase-positive neurons and induced transcription factors tied to dopaminergic differentiation (Hamann et al., 2008). It also protects and regenerates those neurons after toxin exposure, suppresses microglial proliferation and lowers alpha-synuclein (Polanski et al., 2010). In rats it raised complex I activity and induced BDNF, CDNF, CBLN1 and CNTF transcripts (Wernicke et al., 2010). Astrocytes mediate part of the effect through organic cation transport and PI3K signalling, and the compound inhibits monoamine oxidase, IC50 about 1 micromolar for MAO-A and 15.5 micromolar for MAO-B (Keller et al., 2020). Photoexcited 9-methyl-beta-carbolines damage DNA in vitro under UVA (Vignoni et al., 2013). ### Evidence Preclinical: animal or in vitro data only - Raised the number of differentiated dopaminergic neurons and lowered caspase-3 activity in primary mouse mesencephalic culture (Hamann et al., 2008) - Protected dopaminergic neurons against lipopolysaccharide and 2,9-dimethyl-beta-carbolinium toxicity, regenerated them after chronic rotenone, and suppressed toxin-induced microglial proliferation (Polanski et al., 2010) - Fourteen days of intracerebroventricular dosing in MPP+-lesioned rats restored striatal dopamine and nigral tyrosine hydroxylase cell counts, with about 80% higher complex I activity (Wernicke et al., 2010) - Ten days of treatment improved radial-maze spatial learning in rats, with higher hippocampal dopamine and greater dendritic and synaptic density; five days did not (Gruss et al., 2012) - Inhibits monoamine oxidase A at about 1 micromolar and MAO-B at 15.5 micromolar, and stimulates neurotrophic factor expression in astrocytes through PI3K (Keller et al., 2020) - Human-trial status: none. No clinical trial, no human pharmacokinetics and no human safety data; all work is rodent or cell culture, and the in vivo rat studies used intracerebroventricular delivery ### References - [9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture. Hamann J, Wernicke C, Lehmann J, et al., Neurochemistry International, 2008](https://doi.org/10.1016/j.neuint.2007.08.018) - [The exceptional properties of 9-methyl-beta-carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti-inflammatory effects. Polanski W, Enzensperger C, Reichmann H, Gille G, Journal of Neurochemistry, 2010](https://doi.org/10.1111/j.1471-4159.2010.06725.x) - [9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease. Wernicke C, Hellmann J, Zieba B, et al., Pharmacological Reports, 2010](https://doi.org/10.1016/s1734-1140(10)70241-3) - [9-Methyl-beta-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation. Gruss M, Appenroth D, Flubacher A, et al., Journal of Neurochemistry, 2012](https://doi.org/10.1111/j.1471-4159.2012.07713.x) - [9-Methyl-beta-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes. Keller S, Polanski WH, Enzensperger C, et al., Journal of Neural Transmission, 2020](https://doi.org/10.1007/s00702-020-02189-9) - [Mechanisms of DNA damage by photoexcited 9-methyl-beta-carbolines. Vignoni M, Rasse-Suriani FA, Butzbach K, et al., Organic and Biomolecular Chemistry, 2013](https://doi.org/10.1039/c3ob40344k) - [Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-beta-carboline: a new anti-Parkinson drug?. Polanski W, Reichmann H, Gille G, Expert Review of Neurotherapeutics, 2011](https://doi.org/10.1586/ern.11.1) ### Side effects No human safety data; effects unknown beyond animal studies in rodents. Beta-carbolines inhibit monoamine oxidase at higher concentrations, so combining with SSRIs, MAOIs, stimulants, or tyramine-rich foods poses serotonin syndrome and hypertensive crisis risk. Liver enzyme changes in rodent work make hepatic monitoring prudent. ### Storage - Storage: Room temperature, away from light - Lyophilized: 12+ months ### Pharmacology - Half-life: Not established in any species; no pharmacokinetic study published - Bioavailability: Not measured. Beta-carbolines occur endogenously and in food, and 9-methyl-beta-carboline has been detected in brain and cerebrospinal fluid in the broader literature, but no oral bioavailability or brain-uptake figure exists for the administered compound (Hamann et al., 2008; Keller et al., 2020). - Molecular weight: 182.22 Da - Sequence: N/A - small molecule pyridoindole alkaloid, 9-methylpyrido[3,4-b]indole (PubChem CID 164979) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## ACE-031 URL: https://peptidelabs.app/peptides/ace-031/ Also known as: ActRIIB-Fc, Myostatin decoy receptor Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Soluble ActRIIB-Fc decoy receptor that binds myostatin and related ligands to increase muscle mass; human trials were halted over bleeding side effects. ACE-031 is a recombinant fusion of the extracellular domain of activin receptor type IIB with human IgG1-Fc, developed by Acceleron Pharma as a myostatin trap. In a single-ascending-dose phase 1 study, 48 healthy postmenopausal women received 0.02 to 3 mg/kg subcutaneously or placebo; mean t1/2 was 10 to 15 days, and at 3 mg/kg total lean mass rose 3.3% (DXA, p=0.03) and thigh muscle volume 5.1% (MRI, p=0.03) by day 29 (Attie 2013). A randomized placebo-controlled ascending-dose trial then gave 0.5 mg/kg every 4 weeks or 1 mg/kg every 2 weeks subcutaneously to ambulatory boys with Duchenne muscular dystrophy. It was stopped after the second dosing regimen because of epistaxis and telangiectasia, with only non-significant trends on the 6-minute walk test, lean mass and bone density (Campbell 2017). Development was discontinued; nothing was approved. ### Benefits Total lean mass +3.3% and thigh muscle volume +5.1% at day 29 after one 3 mg/kg dose in healthy postmenopausal women (phase 1, n=48); trends toward higher lean mass, bone density and 6-minute walk distance in Duchenne muscular dystrophy (phase 2). Development stopped for bleeding events. ### Dosing reference - Research dose: 0.5 mg/kg every 4 weeks or 1 mg/kg every 2 weeks subcutaneously in the phase 2 trial (NCT01099761); 0.02 to 3 mg/kg as a single subcutaneous dose in phase 1 - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 1 mg Subcutaneous, not intravenous: 0.5 mg/kg every 4 weeks or 1 mg/kg every 2 weeks every 2 to 4 weeks in boys with Duchenne muscular dystrophy, and 0.02 to 3 mg/kg as a single dose in healthy postmenopausal women. Exposure rose linearly with dose and mean t1/2 was 10 to 15 days (Attie 2013). Development was discontinued after the phase 2 trial was stopped for epistaxis and telangiectasia (Campbell 2017). Weight-based dosing, so the mcg dose fields stay null. ### Mechanism ACE-031 is the extracellular domain of activin receptor type IIB fused to human IgG1-Fc. As a soluble decoy it binds myostatin (GDF-8) and other ActRIIB ligands, including activin A and GDF-11, before they reach the receptor, lifting myostatin's brake on muscle growth (Attie 2013; Campbell 2017). Transgenic expression of a dominant-negative ActRIIB in mouse muscle produced muscle-mass increases comparable to myostatin knockouts, which is the preclinical basis for the approach (Lee and McPherron 2001). The bleeding events that stopped development, epistaxis and telangiectasia, are proposed to come from blocking non-myostatin ActRIIB ligands involved in vascular integrity rather than from the muscle effect; the trial report classes them as non-muscle-related adverse events without assigning a mechanism. ### Evidence Clinical: at least one published human trial or an approved drug - In 48 healthy postmenopausal women given one subcutaneous dose of 0.02 to 3 mg/kg or placebo, exposure rose linearly with dose, mean t1/2 was 10 to 15 days, and the 3 mg/kg group gained 3.3% total lean mass (DXA, p=0.03) and 5.1% thigh muscle volume (MRI, p=0.03) by day 29 (Attie et al., 2013) - The main phase 1 adverse event was injection-site erythema; biomarker changes also suggested effects on bone and fat metabolism (Attie et al., 2013) - In ambulatory boys with Duchenne muscular dystrophy dosed 0.5 mg/kg every 4 weeks or 1 mg/kg every 2 weeks subcutaneously, the trial was stopped after the second dosing regimen because of epistaxis and telangiectasia; 6-minute walk, lean mass, bone density and fat mass showed non-significant trends in favour of treatment (Campbell et al., 2017) - Transgenic mice expressing a dominant-negative ActRIIB in skeletal muscle gained muscle mass comparable to myostatin-knockout mice, the preclinical basis for decoy-receptor blockade (Lee and McPherron, 2001) - Human-trial status: one phase 1 and one phase 2 trial published; development was discontinued on safety grounds and no regulator has approved it ### References - [A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Attie KM, Borgstein NG, Yang Y, et al., Muscle & Nerve, 2013](https://doi.org/10.1002/mus.23539) - [Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Campbell C, McMillan HJ, Mah JK, et al., Muscle & Nerve, 2017](https://doi.org/10.1002/mus.25268) - [Regulation of myostatin activity and muscle growth. Lee SJ, McPherron AC, Proceedings of the National Academy of Sciences, 2001](https://doi.org/10.1073/pnas.151270098) ### Side effects The phase 2 trial in boys with Duchenne muscular dystrophy was stopped after the second dosing regimen because of epistaxis and telangiectasia, and no serious or severe adverse events were recorded before that (Campbell 2017). In the phase 1 single-dose study in 48 healthy postmenopausal women, injection-site erythema was the main adverse event (Attie 2013). Bleeding and dilated surface vessels are the defining safety concern of this compound and the reason development was discontinued. It is not approved for human use. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Mean 10 to 15 days (human, single subcutaneous dose 0.02 to 3 mg/kg; Attie 2013) - Bioavailability: Subcutaneous: AUC and Cmax rose linearly with dose from 0.02 to 3 mg/kg in humans; no absolute bioavailability reported - Molecular weight: 90000 Da - Sequence: ActRIIB extracellular domain fused to IgG1 Fc ### Stacks with - [Follistatin-344](https://peptidelabs.app/peptides/follistatin-344/) - [IGF-1 LR3](https://peptidelabs.app/peptides/igf-1-lr3/) ### Categories - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## Acetyl Hexapeptide-3 (Argireline) URL: https://peptidelabs.app/peptides/acetyl-hexapeptide-3-argireline/ Also known as: Argireline, Acetyl Hexapeptide-8, Acetyl Hexapeptide-8 Amide, Ac-EEMQRR-NH2, AH8 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic acetylated hexapeptide (Ac-EEMQRR-NH2) modelled on the SNAP-25 N-terminus; a 2013 placebo-controlled trial (n=60) found less periorbital wrinkling after 4 weeks of topical use. Argireline (acetyl hexapeptide-3, now INCI acetyl hexapeptide-8) was designed by a Spanish academic and industry group as a topical alternative to botulinum toxin; an O/W emulsion reduced wrinkle depth up to 30% in 30 days in healthy women (Blanes-Mira et al., 2002). Independent trials followed: a randomized placebo-controlled study in 60 Chinese adults found 48.9% global improvement in periorbital lines versus 0% on placebo (Wang et al., 2013), and a four-arm study (n=24) found reduced roughness (Raikou et al., 2017). An FDA lab found only 0.01% of an applied dose in the epidermis of human skin in vitro and none in the dermis (Kraeling et al., 2015), so whether it reaches muscle is unproven. ### Benefits Periorbital wrinkle reduction (human RCT, n=60), skin roughness reduction (small human RCT), neurotransmitter release inhibition (in vitro) ### Dosing reference - Research dose: Topical only. Published studies used an emulsion stated as 10% (Blanes-Mira 2002); the CIR panel found it safe in cosmetics up to 0.005% and data insufficient above that. No oral or injectable dose exists. Topical cream or serum applied to expression lines. Trials ran 4 weeks to 60 days, twice daily. Concentration conventions differ: papers state 10% emulsions, while the CIR safety review covers use up to 0.005% peptide. ### Mechanism Proposed. The peptide copies the N-terminal sequence of SNAP-25 and in cell assays interfered with formation or stability of the SNARE complex, inhibiting calcium-dependent neurotransmitter release with potency similar to botulinum toxin A but much lower efficacy (Blanes-Mira et al., 2002). Whether topical application reaches the neuromuscular junction is unresolved: in human and guinea pig skin in vitro almost all peptide stayed on the surface or in the stratum corneum, with none detected in the dermis (Kraeling et al., 2015). ### Evidence Clinical: at least one published human trial or an approved drug - Wrinkle depth fell up to 30% after 30 days of an O/W emulsion in healthy women; cell work showed SNARE complex interference (Blanes-Mira et al., 2002) - Randomized placebo-controlled trial, 60 Chinese adults, twice daily for 4 weeks: 48.9% global improvement in periorbital lines vs 0% on placebo, roughness reduced on silicone replicas (Wang et al., 2013) - Four-arm randomized study (n=24) over 60 days: acetyl hexapeptide-3 reduced roughness and transepidermal water loss vs no peptide (Raikou et al., 2017) - Randomized double-blind pilot in 24 blepharospasm patients: topical use alongside botulinum toxin gave a non-significant trend to longer symptom control, 3.7 vs 3.0 months (Lungu et al., 2013) - Human-trial status: small topical RCTs only, the first from the developers; no injectable study exists, and one Mycobacterium abscessus infection followed off-label facial injection (Chen et al., 2021) ### References - [A synthetic hexapeptide (Argireline) with antiwrinkle activity. Blanes-Mira C, Clemente J, Jodas G, et al., International Journal of Cosmetic Science, 2002](https://pubmed.ncbi.nlm.nih.gov/18498523/) - [The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study. Wang Y, Wang M, Xiao S, Pan P, et al., American journal of clinical dermatology, 2013](https://doi.org/10.1007/s40257-013-0009-9) - [The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study. Raikou V, Varvaresou A, Panderi I, Papageorgiou E, Journal of cosmetic dermatology, 2017](https://doi.org/10.1111/jocd.12314) - [Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy. Lungu C, Considine E, Zahir S, Ponsati B, et al., European journal of neurology, 2013](https://doi.org/10.1111/ene.12009) - [In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation. Kraeling ME, Zhou W, Wang P, Ogunsola OA, Cutaneous and ocular toxicology, 2015](https://doi.org/10.3109/15569527.2014.894521) - [Safety Assessment of Acetyl Hexapeptide-8 Amide as Used in Cosmetics. Johnson W Jr, Bergfeld WF, Belsito DV, Cohen DE, et al., International journal of toxicology, 2025](https://doi.org/10.1177/10915818251340391) - [The study of cellular cytotoxicity of argireline - an anti-aging peptide. Grosicki M, Latacz G, Szopa A, Cukier A, et al., Acta biochimica Polonica, 2014](https://pubmed.ncbi.nlm.nih.gov/24644551/) - [Mycobacterium abscessus infection after facial injection of argireline: A case report. Chen CF, Liu J, Wang SS, Yao YF, et al., World journal of clinical cases, 2021](https://doi.org/10.12998/wjcc.v9.i8.1996) ### Side effects No significant adverse events in the 24-patient blepharospasm RCT (Lungu et al., 2013); no oral toxicity or primary irritation at high doses in developer tests (Blanes-Mira et al., 2002). Cytotoxic to cultured human cells only far above use levels (Grosicki et al., 2014). The CIR panel found data insufficient above 0.005%. One Mycobacterium abscessus abscess followed facial injection (Chen et al., 2021). Commonly reported (anecdotal): mild stinging or redness. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Topical (human cadaver skin in vitro, 10% O/W emulsion, 24 h): 0.22% of dose in stratum corneum, 0.01% in epidermis, none in dermis or receptor fluid - Molecular weight: 888.99 Da - Sequence: Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## Adamax URL: https://peptidelabs.app/peptides/adamax/ Also known as: Semax analog (unpublished structure) Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Adamantane-modified analog of the ACTH(4-7) peptide Semax, intended for greater lipophilicity and brain uptake; almost no published research exists. Adamax is a research analog of the Russian nootropic peptide Semax (ACTH 4-7 Pro-Gly-Pro) modified with an adamantane group intended to increase lipophilicity and blood-brain-barrier penetration. Unlike Semax itself, Adamax has essentially no peer-reviewed literature of its own; reported cognitive and neuroprotective effects are extrapolated from Semax research and community reports. ### Benefits Extrapolated from Semax research: memory, focus and neuroprotection; no published human or animal data on Adamax itself ### Dosing reference - Research dose: 100 to 500 mcg daily (vendor/community range, no published human dose) - Range: 100 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Routes in circulation are intranasal and subcutaneous, both community convention. No published study has administered this compound, so there is no pharmacokinetic basis for any dose or interval. Parent-compound work used intranasal Semax in rats (Dolotov et al., 2006). ### Mechanism No mechanism has been published for Adamax itself; nothing in PubMed or PubChem describes the compound. Everything stated about it is extrapolated from Semax, the ACTH(4-7)-Pro-Gly-Pro heptapeptide. In rats, Semax raised BDNF and trkB expression in the hippocampus within hours of a single intranasal dose (Dolotov et al., 2006) and changed NGF and BDNF transcript levels in hippocampus, frontal cortex and retina (Shadrina et al., 2010). Transcriptome work after middle cerebral artery occlusion in rats found Semax altered immune and vascular gene sets (Filippenkov et al., 2020). Whether an adamantane or acetyl modification preserves any of this is untested. ### Evidence Anecdotal: no peer-reviewed data - No study of Adamax exists in PubMed under that name or any resolvable synonym (search run 2026-10-05) - Parent compound Semax raised hippocampal BDNF and trkB mRNA in rats after intranasal dosing (Dolotov et al., 2006) - Semax changed NGF and BDNF expression in rat hippocampus, frontal cortex and retina, with different time courses per region (Shadrina et al., 2010) - Semax altered immune and vascular gene expression after cerebral ischaemia-reperfusion in rats (Filippenkov et al., 2020) - Russian clinical reports of Semax in ischaemic stroke exist but are open-label and single-country (Gusev et al., 2018) - Human-trial status: no trial, no pharmacokinetics and no safety study of Adamax in any species; the parent peptide's approvals and trials are Russian and do not transfer to this analog ### References - [Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Dolotov OV, Karpenko EA, Inozemtseva LS, et al., Brain Research, 2006](https://doi.org/10.1016/j.brainres.2006.07.108) - [Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. Shadrina M, Kolomin T, Agapova T, et al., Journal of Molecular Neuroscience, 2010](https://doi.org/10.1007/s12031-009-9270-z) - [The heptapeptide SEMAX stimulates BDNF expression in different areas of the rat brain in vivo. Dolotov OV, Seredenina TS, Levitskaya NG, et al., Doklady Biological Sciences, 2003](https://doi.org/10.1023/a:1025177812262) - [Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Filippenkov IB, Stavchansky VV, Denisova AE, et al., Genes, 2020](https://doi.org/10.3390/genes11060681) - [The efficacy of semax in the tretament of patients at different stages of ischemic stroke. Gusev EI, Martynov MY, Kostenko EV, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018](https://doi.org/10.17116/jnevro20181183261-68) ### Side effects No published human safety data; everything reported about it is extrapolated from Semax. Anecdotal reports mention headache, overstimulation, and irritability. The photosensitivity warning that circulates with this compound is unsourced. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not established in any species; no pharmacokinetic study of this compound exists - Bioavailability: Not measured. No bioavailability data exist for this compound by any route. ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Adipotide (FTPP) URL: https://peptidelabs.app/peptides/adipotide-ftpp/ Also known as: FTPP, Prohibitin-targeting peptide, Prohibitin-TP01 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Proapoptotic peptidomimetic that binds prohibitin on white-fat blood vessels; 4 weeks of daily dosing cut body weight 7 to 15% in obese rhesus monkeys, with reversible kidney tubule effects. Adipotide is CKGGRAKDC, a peptide found by in vivo phage display to home to white-fat vasculature through prohibitin, joined to the proapoptotic D-amino-acid motif (KLAKLAK)2 (Kolonin 2004; Ellerby 1999). In obese mice the conjugate ablated white fat and reversed obesity (Kolonin 2004). In obese rhesus monkeys, 0.43 mg/kg daily for 4 weeks reduced weight 7.4 to 14.7%, cut fat on MRI and DXA, and improved insulin resistance, with predictable, reversible changes in kidney proximal tubule function (Barnhart 2011). A comment argued the monkey weight loss may reflect lower food intake rather than fat-vessel ablation (Criscione 2012). In mice it improved glucose tolerance within days (Kim 2012). A phase 1 trial in men with prostate cancer and obesity enrolled 4 patients and was terminated. ### Benefits Fat-mass reduction and reversal of obesity (mouse), 7 to 15% weight loss and improved insulin resistance (obese rhesus monkeys, 4 weeks), weight-independent improvement in glucose tolerance (obese mice); no human efficacy data ### Dosing reference - Research dose: 0.1 to 0.5 mg daily (community range); the human phase 1 started at 0.03 mg/kg daily and primates received 0.25 to 0.75 mg/kg daily - Range: 100 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Subcutaneous, once daily in all published work. Primate studies: 0.43 mg/kg daily for 28 days in obese rhesus monkeys, 0.25 to 0.75 mg/kg in the lean-monkey toxicology study (Barnhart 2011). Phase 1: 0.03 mg/kg daily for 28 days as a starting dose (NCT01262664). No completed human dosing study. ### Mechanism Adipotide has two domains. CKGGRAKDC binds prohibitin, which Kolonin 2004 established as a marker on the endothelium of white-fat blood vessels. The D-(KLAKLAK)2 motif disrupts mitochondrial membranes once internalised, triggering apoptosis (Ellerby 1999). Targeted apoptosis of fat vasculature leads to resorption of white fat (Kolonin 2004; Barnhart 2011). Reduced food intake may also contribute (Criscione 2012). Renal effects are attributed to proximal tubule exposure; the paper describes them as predictable and reversible (Barnhart 2011). ### Evidence Preclinical: animal or in vitro data only - Targeting a proapoptotic peptide to prohibitin on fat vasculature ablated white fat and reversed obesity in mice (Kolonin et al., 2004) - 0.43 mg/kg subcutaneously daily for 4 weeks reduced body weight 7.4 to 14.7% in 10 obese rhesus monkeys versus +1.0 to -3.5% in 5 controls, and improved insulin resistance (Barnhart et al., 2011) - Renal proximal tubule changes were dose-dependent and reversible; creatinine rose at 0.75 mg/kg in lean monkeys (Barnhart et al., 2011) - Disputed: a published comment argued the monkey weight loss may be driven by reduced food intake (Criscione, 2012) - Human-trial status: one phase 1 (prostate cancer with obesity, starting dose 0.03 mg/kg daily) enrolled 4 patients and was terminated at the investigator's request; no results published (NCT01262664) ### References - [Reversal of obesity by targeted ablation of adipose tissue. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W, Nature Medicine, 2004](https://doi.org/10.1038/nm1048) - [A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Barnhart KF, Christianson DR, Hanley PW, et al., Science Translational Medicine, 2011](https://doi.org/10.1126/scitranslmed.3002621) - [Comment on "a peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys". Criscione L, Science Translational Medicine, 2012](https://doi.org/10.1126/scitranslmed.3003760) - [Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Kim DH, Sartor MA, Bain JR, et al., Diabetes, 2012](https://doi.org/10.2337/db11-1579) - [Anti-cancer activity of targeted pro-apoptotic peptides. Ellerby HM, Arap W, Ellerby LM, et al., Nature Medicine, 1999](https://doi.org/10.1038/12469) ### Side effects No published human safety data; the only human trial enrolled 4 patients and posted no results. In monkeys, kidney proximal tubule function changed in a dose-dependent, reversible way: creatinine rose at 0.75 mg/kg/day and sporadically in 2 animals at 0.43 mg/kg/day, with slight residual creatinine and urine glucose elevation in one monkey per study after recovery (Barnhart 2011). Single doses up to 100 mg/kg were not lethal in monkeys. Dehydration and reduced appetite are commonly reported (anecdotal). ### Storage - Storage: Refrigerate 2-8°C (36-46°F); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not published in any species; primate studies dosed once daily subcutaneously (Barnhart 2011) - Bioavailability: Not reported. Primate efficacy studies used subcutaneous injection (Barnhart 2011); the human phase 1 used subcutaneous dosing - Molecular weight: 2557.2 Da - Sequence: CKGGRAKDCGG[D-KLAKLAKKLAKLAK] ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## AHK URL: https://peptidelabs.app/peptides/ahk/ Also known as: Alanine-Histidine-Lysine, AHK tripeptide, Ala-His-Lys Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Tripeptide Ala-His-Lys; no published study tests the free peptide. Its copper complex AHK-Cu has ex vivo human hair follicle data and its own catalog entry. AHK (Ala-His-Lys) is a tripeptide sold for hair and skin products. Every hair study found used its copper complex, AHK-Cu, tested on human hair follicles ex vivo (Pyo 2007); a 2026 review lists only ex vivo data (Fan 2026). Those results belong to the AHK-Cu entry and do not transfer to the free peptide. The only other paper used a vitamin C-linker conjugate of AHK in mouse myoblast cells (Jung 2018). No human trial exists for AHK in any form. ### Benefits None published for free AHK. The copper complex AHK-Cu has ex vivo human hair follicle data (see AHK-Cu entry) ### Dosing reference - Research dose: Topical application Topical. No published concentration or dose for the free tripeptide. ### Mechanism Unknown for the free peptide. The old text's VEGF, Wnt and anagen claims came from GHK-Cu and AHK-Cu without a source. AHK binds copper to form AHK-Cu, which was tested on human hair follicles ex vivo (Pyo 2007); see that entry. A vitamin C-linker conjugate of AHK stimulated BMP-2-induced osteogenic differentiation in mouse C2C12 cells (Jung 2018). ### Evidence Anecdotal: no peer-reviewed data - No published study of free AHK in any model - A vitamin C-linker conjugate of AHK stimulated BMP-2-induced osteogenic differentiation of mouse C2C12 myoblasts (Jung et al., 2018) - Human-trial status: none. Only the copper complex AHK-Cu has hair data, on human follicles ex vivo, with a non-significant change in apoptosis (Pyo et al., 2007; Fan et al., 2026); see the AHK-Cu entry ### References - [The effect of tripeptide-copper complex on human hair growth in vitro. Pyo HK, Yoo HG, Won CH, Lee SH, et al., Archives of Pharmacal Research, 2007](https://doi.org/10.1007/BF02978833) - [Overview of Short Peptides for Hair Loss. Fan C, Chen Y, Huang Q, Ou WY, et al., Biomedicines, 2026](https://doi.org/10.3390/biomedicines14040864) - [Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells. Jung JI, Park KY, Lee Y, Park M, et al., Differentiation, 2018](https://doi.org/10.1016/j.diff.2018.03.001) ### Side effects No published safety data for the free tripeptide in any species. Commonly reported (anecdotal): irritation, redness or stinging with topical peptide products. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured; no skin penetration study of the free tripeptide has been published - Molecular weight: 354.41 Da - Sequence: Ala-His-Lys ### Categories - [Hair Growth](https://peptidelabs.app/peptides/category/hair-growth/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) ## AHK-Cu (Copper Peptide) URL: https://peptidelabs.app/peptides/ahk-cu-copper-peptide/ Also known as: AHK Copper, AHK-Cu2+, L-alanyl-L-histidyl-L-lysine copper(II) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Copper(II) complex of the tripeptide Ala-His-Lys; one ex vivo study found it lengthened human hair follicles in organ culture and raised dermal papilla cell proliferation. AHK-Cu is the copper(II) complex of L-alanyl-L-histidyl-L-lysine, a close analog of GHK-Cu (separate catalog entry) with alanine in place of glycine. The one peer-reviewed study found that 1 pM to 1 nM AHK-Cu lengthened isolated human hair follicles in organ culture and increased dermal papilla cell proliferation, with a higher Bcl-2/Bax ratio and less cleaved caspase-3 (Pyo et al., 2007). No animal or human study of hair growth has been published. Claims of better scalp circulation and synergy from copper binding have no published source. The uncomplexed peptide is catalogued separately as AHK. ### Benefits Hair follicle elongation (ex vivo human follicles), dermal papilla cell proliferation and reduced apoptosis markers (in vitro) ### Dosing reference - Research dose: Topical only; no published study gives a formulation concentration for skin or scalp. Ex vivo work used 1 pM to 1 nM in culture medium. Sold for topical scalp use. No human or animal dosing study exists; the ex vivo concentrations (1 pM to 1 nM) do not translate to a formulation strength. ### Mechanism Proposed, from one ex vivo study. In cultured human dermal papilla cells AHK-Cu increased proliferation, raised the Bcl-2/Bax ratio and lowered cleaved caspase-3 and PARP, suggesting reduced apoptosis; it lengthened isolated follicles at 1 pM to 1 nM (Pyo et al., 2007). The same paper cites earlier work on copper tripeptides raising VEGF in dermal fibroblasts, but VEGF was not measured for AHK-Cu itself. Anagen extension, DHT inhibition and pigmentation effects have no published data for this compound. ### Evidence Preclinical: animal or in vitro data only - AHK-Cu at 1 pM to 1 nM lengthened human hair follicles in ex vivo organ culture (Pyo et al., 2007) - Raised dermal papilla cell proliferation in vitro; at 1 nM the Bcl-2/Bax ratio rose and cleaved caspase-3 and PARP fell (Pyo et al., 2007) - Human-trial status: no animal or human study of AHK-Cu has been published; the only peer-reviewed evidence is one ex vivo and cell study ### References - [The effect of tripeptide-copper complex on human hair growth in vitro. Pyo HK, Yoo HG, Won CH, Lee SH, et al., Archives of pharmacal research, 2007](https://doi.org/10.1007/BF02978833) ### Side effects No safety study in animals or humans has been published; the one ex vivo study was not designed to detect harm. No injectable data exist. Commonly reported (anecdotal): scalp irritation and a temporary blue-green tint from copper complexes. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species; follicle or skin penetration of AHK-Cu has not been studied - Molecular weight: 415.94 Da - Sequence: AHK (Ala-His-Lys), copper(II) complex ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Hair Growth](https://peptidelabs.app/peptides/category/hair-growth/) ## AICAR URL: https://peptidelabs.app/peptides/aicar/ Also known as: Acadesine, AICA riboside, AICAr, 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, ARA 100, GP 1 110 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Nucleoside AMPK activator (AICA riboside) that mimics exercise signalling, increasing glucose uptake, fat oxidation and running endurance in mice. AICAR (acadesine, AICA riboside) is a nucleoside that is phosphorylated inside cells to ZMP, an AMP mimetic that activates AMPK. In sedentary mice, 4 weeks of AICAR raised running endurance 44% and induced oxidative metabolic genes (Narkar 2008). Human work is all intravenous: in 10 men with type 2 diabetes an infusion lowered hepatic glucose output and suppressed whole-body lipolysis (Boon 2008); muscle 2-deoxyglucose uptake rose 1.6 to 2.9-fold, less in older men (Babraj 2009); under a hyperinsulinaemic clamp it raised heart rate and lowered blood pressure with no added glucose uptake (Bosselaar 2011). It was developed as a cardioprotective agent and failed a 3080-patient cardiac surgery RCT (Newman 2012), and reached phase 1/2 in leukaemia (Van Den Neste 2013). Not approved anywhere; prohibited in sport. ### Benefits Running endurance and fat oxidation (mouse), lower hepatic glucose output and suppressed lipolysis (human IV infusion), prohibited in sport ### Dosing reference - Research dose: 150-500 mg daily (research-community range; no published human study used this dose or the subcutaneous route) - Range: 150000 to 500000 mcg, 1x daily - Reconstitution: 3 mL bacteriostatic water - Common vial sizes: 50 mg Human studies used intravenous dosing only: 10-100 mg/kg single doses in healthy men (Dixon 1991), 0.75 mg/kg/min continuous infusion in type 2 diabetes (Boon 2008), 10-20 mg/kg/h for 3 h (Babraj 2009), 50-315 mg/kg (210 mg/kg was the maximum tolerated dose) over 4 h in leukaemia with 210 mg/kg as the maximum tolerated dose (Van Den Neste 2013) and 0.1 mg/kg/min for 7 h in cardiac surgery (Newman 2012). Oral solution is under 5% bioavailable (Dixon 1991). The mouse endurance work used 4 weeks of daily injection (Narkar 2008). AICAR is prohibited in sport and urinary concentrations above about 2000 ng/mL trigger isotope-ratio confirmation (Sobolevsky 2019). ### Mechanism AICAR is taken into cells by nucleoside transporters and phosphorylated by adenosine kinase to ZMP, which mimics AMP and activates AMP-activated protein kinase (Narkar 2008). In mice, 4 weeks of treatment induced an oxidative gene program through AMPK and PPAR-delta and raised running endurance without training (Narkar 2008). In humans, AICAR infusion reduced hepatic glucose output and plasma NEFA appearance and raised acetyl-CoA carboxylase phosphorylation in muscle, while muscle AMPK phosphorylation itself did not rise (Boon 2008); muscle glucose uptake rose with ERK1/2 rather than AMPK activation (Babraj 2009). It also causes systemic vasodilation, probably nitric-oxide dependent (Bosselaar 2011), and has documented AMPK-independent actions. Not a peptide; included for reference. ### Evidence Preclinical: animal or in vitro data only - Four weeks of AICAR in sedentary mice raised treadmill running endurance 44% and induced oxidative metabolic genes (Narkar et al., 2008) - IV infusion (0.75 mg/kg/min) in 10 men with type 2 diabetes reduced hepatic glucose output and suppressed whole-body lipolysis (Boon et al., 2008) - IV AICAR (10-20 mg/kg/h) raised muscle 2-deoxyglucose uptake 2.9-fold in young men and 1.6-1.8-fold in older men and men with type 2 diabetes, without detectable muscle AMPK activation (Babraj et al., 2009) - Under a hyperinsulinaemic clamp in 10 healthy adults, AICAR (67 mg/kg) raised heart rate and lowered blood pressure but did not increase glucose uptake (Bosselaar et al., 2011) - RED-CABG, 3080 patients undergoing on-pump bypass surgery: a 7-hour infusion did not reduce death, stroke or severe left ventricular dysfunction at 28 days (Newman et al., 2012) - Human-trial status: phase 1 PK in healthy men (Dixon 1991), a phase 1/2 leukaemia study with a 210 mg/kg maximum tolerated dose (Van Den Neste et al., 2013) and a negative phase 3 cardiac surgery RCT. No approval anywhere and no human trial of the endurance or body-composition uses ### References - [AMPK and PPARdelta agonists are exercise mimetics. Narkar VA, Downes M, Yu RT, et al., Cell, 2008](https://doi.org/10.1016/j.cell.2008.06.051) - [AICA-riboside: safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent. Dixon R, Gourzis J, McDermott D, Fujitaki J, Dewland P, Gruber H, Journal of Clinical Pharmacology, 1991](https://doi.org/10.1002/j.1552-4604.1991.tb03715.x) - [Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Boon H, Bosselaar M, Praet SF, et al., Diabetologia, 2008](https://doi.org/10.1007/s00125-008-1108-7) - [Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status. Babraj JA, Mustard K, Sutherland C, et al., American Journal of Physiology - Endocrinology and Metabolism, 2009](https://doi.org/10.1152/ajpendo.90811.2008) - [Intravenous AICAR during hyperinsulinemia induces systemic hemodynamic changes but has no local metabolic effect. Bosselaar M, Smits P, van Loon LJ, Tack CJ, Journal of Clinical Pharmacology, 2011](https://doi.org/10.1177/0091270010382912) - [Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. Newman MF, Ferguson TB, White JA, et al., JAMA, 2012](https://doi.org/10.1001/jama.2012.7633) - [Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study. Van Den Neste E, Cazin B, Janssens A, et al., Cancer Chemotherapy and Pharmacology, 2013](https://doi.org/10.1007/s00280-012-2033-5) - [Urinary concentrations of AICAR and mannitol in athlete population. Sobolevsky T, Ahrens B, Drug Testing and Analysis, 2019](https://doi.org/10.1002/dta.2557) ### Side effects Human IV studies report transient infusion-related hypotension with a rise in heart rate (Bosselaar 2011), grade 2 or higher hyperuricaemia, transient anaemia or thrombocytopenia and renal impairment at 50-210 mg/kg (Van Den Neste 2013), and mild transient effects at 10-100 mg/kg in healthy men (Dixon 1991). The 3080-patient cardiac surgery RCT found no excess of serious adverse events (Newman 2012). There is no oral or chronic human data, and the effects of sustained AMPK activation in humans are unknown. AICAR is prohibited in sport (Sobolevsky 2019). ### Storage - Storage: Refrigerate 2-8°C (36-46°F); general lyophilised-powder guidance, no compound-specific CoA located - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~1.4 h terminal (human, IV; harmonic mean t1/2-beta across 10-100 mg/kg, n=16; Dixon 1991) - Bioavailability: Oral <5% in solution (human; Dixon 1991). Not protein bound, taken up rapidly by erythrocytes and phosphorylated to ZMP (human; Dixon 1991, Bosselaar 2011). No subcutaneous bioavailability data. - Molecular weight: 258.23 Da - Sequence: N/A - nucleoside analog (not a peptide) ### Stacks with - [GW501516](https://peptidelabs.app/peptides/gw501516/) - [MOTS-c](https://peptidelabs.app/peptides/mots-c/) ### Categories - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## Alpha-MSH URL: https://peptidelabs.app/peptides/alpha-msh/ Also known as: α-MSH, Alpha-melanocyte-stimulating hormone, POMC(138-150) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Endogenous 13-residue POMC peptide that activates MC1, MC3, MC4 and MC5 receptors; injected, it changed human skin colour in a small 1961 study. Other effects are from animal models. Alpha-MSH is residues 138 to 150 of proopiomelanocortin (POMC), N-terminally acetylated and C-terminally amidated, made in the pituitary, brain and skin. Injected alpha- and beta-MSH changed skin colour in volunteers in 1961, and a single 2.5 mg IV dose altered LH secretion in 8 women in 1994; no therapeutic trial of the native peptide has been published. Serum enzymes degrade it, which is why stabilized analogs were made: afamelanotide (Melanotan 1, an approved implant for erythropoietic protoporphyria), Melanotan II and bremelanotide (PT-141) are separate catalog entries, as is its C-terminal tripeptide KPV. Anti-inflammatory and appetite effects come from animal and cell models. ### Benefits Skin darkening (small uncontrolled human study, 1961), reduced food intake via MC4R (mouse genetics), anti-inflammatory effects (animal and cell models) ### Dosing reference - Research dose: 50 to 200 mcg daily: vendor/community range, no published human dose. The only modern human dosing was a single 2.5 mg IV bolus - Range: 50 to 200 mcg, 1x daily No dosing study exists. The one modern human exposure was a single 2.5 mg IV bolus in 8 women for endocrine research. The route, frequency and cycle used by vendors have no published basis. ### Mechanism Alpha-MSH is cleaved from POMC and acts on melanocortin receptors, a G protein-coupled family first cloned in 1992 alongside the separate ACTH receptor (Mountjoy et al., 1992). MC1R on melanocytes drives eumelanin synthesis. Central MC4R controls feeding: mice lacking MC4R develop obesity with hyperphagia (Huszar et al., 1997). Anti-inflammatory actions include reduced NF-kB activation and pro-inflammatory cytokines and increased IL-10, shown in cell and animal models of dermatitis, colitis, arthritis and fever (Brzoska et al., 2008). Native alpha-MSH is degraded by serum enzymes, and N-terminal acetylation slows its clearance in rabbits (Rudman et al., 1983). ### Evidence Preclinical: animal or in vitro data only - Injected alpha- and beta-MSH changed skin colour in human volunteers in an uncontrolled study (Lerner and McGuire, 1961) - Cloning of the human and mouse MSH receptor and the human ACTH receptor defined the melanocortin receptor family (Mountjoy et al., 1992) - Targeted deletion of MC4R caused maturity-onset obesity with hyperphagia, hyperinsulinemia and hyperglycemia in mice (Huszar et al., 1997) - Anti-inflammatory effects in animal models of fever, contact dermatitis, colitis, arthritis and organ injury (Brzoska et al., 2008) - A single 2.5 mg IV bolus in 8 women in the luteal phase raised LH and blunted CRH suppression of LH, without changing ACTH or cortisol (Limone et al., 1994) - Human-trial status: no therapeutic trial of native alpha-MSH has been published. Human efficacy data belong to stabilized analogs, chiefly afamelanotide (approved implant, EU 2014, US 2019) and bremelanotide (approved 2019); see those entries ### References - [Effect of alpha- and beta-melanocyte stimulating hormones on the skin colour of man. Lerner AB, McGuire JS, Nature, 1961](https://doi.org/10.1038/189176a0) - [The cloning of a family of genes that encode the melanocortin receptors. Mountjoy KG, Robbins LS, Mortrud MT, et al., Science, 1992](https://doi.org/10.1126/science.1325670) - [Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Huszar D, Lynch CA, Fairchild-Huntress V, et al., Cell, 1997](https://doi.org/10.1016/s0092-8674(00)81865-6) - [Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Brzoska T, Luger TA, Maaser C, et al., Endocrine Reviews, 2008](https://doi.org/10.1210/er.2007-0027) - [Three types of alpha-melanocyte-stimulating hormone: bioactivities and half-lives. Rudman D, Hollins BM, Kutner MH, et al., The American Journal of Physiology, 1983](https://doi.org/10.1152/ajpendo.1983.245.1.E47) - [4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Sawyer TK, Sanfilippo PJ, Hruby VJ, et al., Proceedings of the National Academy of Sciences of the United States of America, 1980](https://doi.org/10.1073/pnas.77.10.5754) - [Alpha-melanocyte-stimulating hormone antagonizes the inhibitory effect of corticotropin-releasing hormone on luteinizing hormone secretion during the luteal phase in normal women. Limone P, Scipioni T, Calvelli P, et al., The Journal of Clinical Endocrinology and Metabolism, 1994](https://doi.org/10.1210/jcem.79.2.8045978) ### Side effects No human safety study of repeated dosing exists. Skin colour change was the effect reported after injection in 1961 (Lerner and McGuire, 1961); the 1994 single IV dose study reported endocrine changes only (Limone et al., 1994). Nausea, flushing and darkening of moles are seen with the analogs and are plausible but not measured for native alpha-MSH. Commonly reported (anecdotal): nausea, flushing. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: Not measured in humans. In rabbit plasma (in vitro and IV) desacetyl alpha-MSH cleared fastest and diacetyl slowest; native peptide is degraded by serum enzymes - Bioavailability: Not measured by any route in any species. Native alpha-MSH is degraded by serum enzymes, unlike its [Nle4,D-Phe7] analog - Molecular weight: 1664.9 Da - Sequence: [Ac-S]YSMEHFRWGKPV[NH2] ### Categories - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## AOD9604 URL: https://peptidelabs.app/peptides/aod9604/ Also known as: AOD-9604, AOD 9604, Tyr-hGH(177-191), Anti-Obesity Drug 9604, sh-Oligopeptide-74 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Modified hGH fragment (Tyr plus hGH 177-191) that reduced weight gain and raised fat oxidation in obese rodents; six human trials found no IGF-1 or glucose effects, with efficacy results unpublished. AOD9604 is tyrosine-hGH(177-191), a synthetic analog of the C-terminal lipolytic region of human growth hormone developed at Monash University and Metabolic Pharmaceuticals. In obese mice and Zucker rats it reduced weight gain, raised fat oxidation and lipolysis, and unlike hGH did not cause insulin resistance or bind the GH receptor (Ng 2000; Heffernan 2001). Six randomised placebo-controlled human trials in about 900 adults used IV doses of 25 to 400 mcg/kg or oral doses of 0.25 to 54 mg; the published summary reports safety only: no change in IGF-1 or glucose tolerance and no antibodies (Stier 2013). Weight-loss results of the 12- and 24-week trials were never published in a peer-reviewed journal. Intra-articular injection aided cartilage repair in a rabbit osteoarthritis model (Kwon 2015). WADA prohibits it. ### Benefits Reduced body weight gain and increased fat oxidation and lipolysis (obese mice and rats), cartilage regeneration after intra-articular injection (rabbit); no effect on IGF-1 or glucose tolerance (human RCTs, safety data only) ### Dosing reference - Research dose: 300 to 500 mcg once daily subcutaneously (community range); human trials used oral 0.25 to 30 mg daily or single IV doses of 25 to 400 mcg/kg - Range: 300 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Community protocols inject 300 to 500 mcg subcutaneously, often fasted in the morning. All published human dosing was oral (capsules 1 to 54 mg; tablets 0.25 to 1 mg for 24 weeks) or single IV infusions of 25 to 400 mcg/kg over 20 minutes (Stier 2013). No subcutaneous human study exists. ### Mechanism AOD9604 corresponds to the C-terminal region of hGH that carries its lipolytic and antilipogenic activity. In rodent adipose tissue it increased lipolysis and reduced lipogenesis (Ng 2000). Its effect on weight is not mediated through the beta-3 adrenergic receptor, although it raises beta-3 receptor expression, and it still raised fat oxidation acutely in beta-3 knockout mice (Heffernan 2001, Endocrinology). It does not compete for the hGH receptor or drive hGH-receptor cell proliferation (Heffernan 2001, Int J Obes). In serum it is degraded to a stable CRSVEGSCG fragment (Cox 2015). Its receptor is not identified. Chondroprotective effects are proposed from one rabbit study (Kwon 2015). ### Evidence Preclinical: animal or in vitro data only - Reduced body weight gain and raised fat oxidation and plasma glycerol in obese mice over 14 days without hyperglycaemia or hGH-receptor binding (Heffernan et al., 2001) - Oral 500 mcg/kg daily for 19 days halved weight gain in obese Zucker rats without impairing insulin sensitivity (Ng et al., 2000) - Six placebo-controlled human trials (about 900 adults; IV 25 to 400 mcg/kg, oral 0.25 to 54 mg daily up to 24 weeks): no change in IGF-1 or glucose tolerance, no antibodies, adverse events similar to placebo (Stier et al., 2013) - Weekly intra-articular 0.25 mg improved cartilage scores in a rabbit osteoarthritis model, more so with hyaluronic acid (Kwon et al., 2015) - Human-trial status: obesity programme ended without published efficacy results; no registered trial is active. A 2013 GRAS determination was by an industry-commissioned panel, not FDA ### References - [Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Ng FM, Sun J, Sharma L, et al., Hormone Research, 2000](https://doi.org/10.1159/000053183) - [The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Heffernan M, Summers RJ, Thorburn A, et al., Endocrinology, 2001](https://doi.org/10.1210/endo.142.12.8522) - [Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan MA, Thorburn AW, Fam B, et al., International Journal of Obesity and Related Metabolic Disorders, 2001](https://doi.org/10.1038/sj.ijo.0801740) - [Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Stier H, Vos E, Kenley D, Journal of Endocrinology and Metabolism, 2013](https://doi.org/10.4021/jem157w) - [Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Kwon DR, Park GY, Annals of Clinical and Laboratory Science, 2015](https://pubmed.ncbi.nlm.nih.gov/26275694/) - [Detection and in vitro metabolism of AOD9604. Cox HD, Smeal SJ, Hughes CM, et al., Drug Testing and Analysis, 2015](https://doi.org/10.1002/dta.1715) - [Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Mendias CL, Awan TM, Sports Medicine, 2026](https://doi.org/10.1007/s40279-026-02437-0) ### Side effects In six placebo-controlled trials (Stier 2013), headache was the most common event, followed by diarrhoea, flatulence and nausea, at rates similar to placebo; 54 mg oral doses produced more headache and GI upset. Mild euphoria was reported by 5 of 23 subjects after IV dosing and not with placebo. IGF-1, glucose tolerance, ECG and safety labs did not change and no anti-AOD9604 antibodies were found. Five cancers (skin, breast, melanoma) arose in the 12-week trial and were judged unrelated by investigators. Injection-site irritation is commonly reported with subcutaneous use (anecdotal); no subcutaneous human data exist. Regulatory: AOD-9604 is in the 503A withdrawn-nomination table of FDA's compounding safety-risk page, page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Storage - Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No human PK published; the parent peptide degraded in serum and urine in vitro, leaving a stable CRSVEGSCG metabolite (Cox 2015) - Bioavailability: Not reported. Oral dosing was active in obese rodents (Ng 2000) and used in all long human trials (Stier 2013); no subcutaneous PK data - Molecular weight: 1815.1 Da - Sequence: YLRIVQCRSVEGSCGF [disulfide Cys7-Cys14] ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## ARA-290 URL: https://peptidelabs.app/peptides/ara-290/ Also known as: Cibinetide, ARA290, pHBSP, pyroglutamate helix B surface peptide, 1208243-50-8 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic 11-amino-acid peptide derived from the helix-B region of erythropoietin that activates the innate repair receptor without EPO's blood-cell effects. ARA-290 (cibinetide, pyroglutamate helix B surface peptide) is an 11-residue peptide modelled on the aqueous face of helix B of erythropoietin. It activates the innate repair receptor, a heterocomplex of the EPO receptor and the beta common receptor induced on injured tissue, without binding the EPO receptor homodimer, so it is not erythropoietic (Brines 2008). Four phase 2 trials are published. In sarcoid small fiber neuropathy, 2 mg IV three times weekly for 4 weeks (n=22) improved the symptom score against placebo (Heij 2012), 4 mg/day subcutaneously for 28 days improved symptoms, corneal nerve fiber density and 6-minute walk distance (Dahan 2013), and a 64-subject dose-ranging trial found 4 mg/day raised corneal nerve fiber area while 1 and 8 mg/day did not (Culver 2017). In type 2 diabetes, 4 mg/day for 28 days improved HbA1c, lipids and PainDetect scores (n=24; Brines 2015). ### Benefits Improved neuropathy symptom scores and corneal small nerve fiber density in phase 2 trials (human RCT, n=22 to 64); improved HbA1c and lipids in type 2 diabetes (human RCT, n=24); tissue protection in stroke, renal ischemia and nerve injury models (animal) ### Dosing reference - Research dose: 1 to 8 mg daily subcutaneously in phase 2 trials, with 4 mg/day the dose that separated from placebo; one trial used 2 mg IV three times weekly - Range: 1000 to 8000 mcg, 1x daily Subcutaneous once daily in most trials, for 28 days; one trial used 2 mg IV three times weekly for 4 weeks. The dose response is not monotonic: in the 64-subject phase 2b, 4 mg/day raised corneal nerve fiber area while 1 and 8 mg/day did not. Plasma half-life is about 2 min, yet the biological effects persist for days (Collino 2015). ### Mechanism Erythropoietin has two separable jobs through two receptors: red cell production via the EPO receptor homodimer, and tissue protection via the innate repair receptor, a heterocomplex of the EPO receptor and CD131 (the beta common receptor) that is not normally expressed but is induced by injury or inflammation. ARA-290 is an 11-residue peptide reproducing the aqueous surface of helix B, which does not contact the homodimer; it activates the innate repair receptor selectively and was tissue-protective in stroke, renal ischemia-reperfusion, retinal edema and peripheral nerve trauma models while showing no erythropoietic activity in vitro or in vivo (Brines 2008). Despite a plasma half-life of about 2 min, the receptor activation triggers effects lasting days, which the developers describe as a molecular switch rather than sustained occupancy (Collino 2015). ### Evidence Clinical: at least one published human trial or an approved drug - An 11-residue peptide reproducing the aqueous face of EPO helix B was tissue-protective in stroke, renal ischemia-reperfusion, retinal edema and nerve trauma models and was not erythropoietic in vitro or in vivo (Brines et al., 2008) - In sarcoidosis with small fiber neuropathy symptoms, 2 mg IV three times weekly for 4 weeks improved the neuropathy screening score against placebo (n=22, randomized double-blind; Heij et al., 2012) - In documented small nerve fiber loss, 28 days of 4 mg/day subcutaneously improved symptoms, corneal small nerve fiber density and 6-minute walk distance against placebo (Dahan et al., 2013) - A 64-subject phase 2b dose-ranging trial found 4 mg/day significantly increased corneal nerve fiber area (placebo-corrected +697 micrometres squared, p=0.012) while 1 and 8 mg/day did not (Culver et al., 2017) - In type 2 diabetes with painful neuropathy, 4 mg/day for 28 days improved HbA1c, lipid profile and PainDetect scores over 56 days of observation (n=24; Brines et al., 2015) - Human-trial status: several completed phase 2 trials, all small (n=22 to 64) and mostly in sarcoid or diabetic small fiber neuropathy. No phase 3 trial and no regulatory approval in any country ### References - [Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Brines M, Patel NS, Villa P, et al., PNAS, 2008](https://doi.org/10.1073/pnas.0805594105) - [Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Heij L, Niesters M, Swartjes M, et al., Molecular Medicine, 2012](https://doi.org/10.2119/molmed.2012.00332) - [ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Dahan A, Dunne A, Swartjes M, et al., Molecular Medicine, 2013](https://doi.org/10.2119/molmed.2013.00122) - [Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. Culver DA, Dahan A, Bajorunas D, et al., Investigative Ophthalmology and Visual Science, 2017](https://doi.org/10.1167/iovs.16-21291) - [ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Brines M, Dunne AN, van Velzen M, et al., Molecular Medicine, 2015](https://doi.org/10.2119/molmed.2014.00215) - [Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Collino M, Thiemermann C, Cerami A, Brines M, Pharmacology and Therapeutics, 2015](https://doi.org/10.1016/j.pharmthera.2015.02.005) ### Side effects Well tolerated in small trials for neuropathic pain, where injection-site reactions were the main finding. Unlike erythropoietin it did not raise hematocrit or blood pressure in the studies conducted. Long-term safety data is limited. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: About 2 min (human, plasma), with biological effects lasting days (Collino 2015) - Molecular weight: 1257.3 Da - Sequence: [Pyr]-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser ([Pyr] = pyroglutamate; 11 aa) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## B7-33 URL: https://peptidelabs.app/peptides/b7-33/ Also known as: B7-33, Relaxin B7-33, single-chain relaxin-2 B-chain analog Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Single-chain 27-residue mimetic of the human relaxin-2 B chain that biases RXFP1 signaling toward pERK; reduced cardiac and lung fibrosis in rodent models. B7-33 is a single-chain 27-residue peptide from the B chain of human relaxin-2 (serelaxin): six residues were cut from the N-terminus of B1-33 and both cysteines replaced with serines to stop dimerization, giving a soluble linear peptide instead of the two-chain, three-disulfide hormone (Hossain 2016). It binds RXFP1 and preferentially activates pERK1/2 over cAMP, the first functionally selective agonist of that receptor. In rodents it prevented or reversed heart and lung fibrosis at relaxin-like potency (0.25 mg/kg/day), cut infarct size in mouse ischemia-reperfusion (22% versus 45%) and matched relaxin for left ventricular fibrosis in isoprenaline cardiomyopathy (Devarakonda 2020; Alam 2023). Unlike relaxin it did not promote prostate tumor growth in mice. No human study is published or registered. ### Benefits Reduced cardiac and lung fibrosis in rodent models at relaxin-equivalent potency; smaller infarct and preserved cardiac function in mouse ischemia-reperfusion (rodent); endothelium-dependent vasodilation matching serelaxin (rat). No human data ### Dosing reference - Research dose: 1 to 10 mg: vendor and community range, no published human dose. Animal studies used 0.25 to 0.5 mg/kg/day subcutaneously in mice and a 13.3 mcg/kg IV bolus in rats - Range: 1000 to 10000 mcg, 1x daily Subcutaneous in research use. Animal dosing was continuous: 0.25 to 0.5 mg/kg/day by implanted osmotic minipump in mice, or a single 13.3 mcg/kg IV bolus in rats. In vitro serum half-life is about 6 min, so a once-daily injection has no published basis. No human pharmacokinetic or safety data exist. ### Mechanism Relaxin-2 acts through RXFP1, a GPCR that couples to both cAMP and ERK1/2. The cAMP arm is linked to the tumor-promoting effects reported for relaxin, so B7-33 was designed to bias signaling: it binds RXFP1 and preferentially phosphorylates ERK1/2 with little cAMP response in cells that express RXFP1 endogenously (Hossain 2016). The antifibrotic effect runs through RXFP1-angiotensin II type 2 receptor heterodimers, driving pERK1/2 and the collagen-degrading enzyme MMP-2. In rat mesenteric artery it enhanced bradykinin-mediated endothelium-dependent relaxation through endothelium-derived hyperpolarization, matching serelaxin at equimolar dose (Marshall 2017). Serum stability is the practical limit: half-life in serum in vitro is about 6 min, which lipidated analogs extend to about 60 min (Praveen 2023). ### Evidence Preclinical: animal or in vitro data only - B7-33 bound RXFP1 and preferentially activated pERK over cAMP, and at 0.25 mg/kg/day subcutaneously prevented or reversed fibrosis and dysfunction in three rodent models of heart and lung disease with potency similar to relaxin, without promoting prostate tumor growth in mice (Hossain et al., 2016) - In mouse myocardial ischemia-reperfusion, B7-33 reduced infarct size (22.0% versus 45.3%, p=0.02) and preserved fractional shortening at 24 h and 7 days (Devarakonda et al., 2020) - In isoprenaline-induced cardiomyopathy in mice, B7-33 at 0.25 mg/kg/day matched relaxin for reducing left ventricular fibrosis, inflammation and hypertrophy, and reduced fibrosis faster than perindopril (Alam et al., 2023) - A single IV bolus of 13.3 mcg/kg in rats reproduced the acute vascular effects of serelaxin in mesenteric artery, and 15 to 30 nM prevented trophoblast-induced endothelial dysfunction in mouse arteries ex vivo (Marshall et al., 2017) - In vitro serum half-life is about 6 min; fatty-acid conjugation extended it to about 60 min in analogs that have not been tested in animals (Praveen et al., 2023) - Human-trial status: none. No trial of B7-33 is published or registered on ClinicalTrials.gov; all data are rodent and in vitro ### References - [A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1. Hossain MA, Kocan M, Yao ST, et al., Chemical Science, 2016](https://doi.org/10.1039/c5sc04754d) - [B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice. Devarakonda T, Mauro AG, Guzman G, et al., Journal of the American Heart Association, 2020](https://doi.org/10.1161/JAHA.119.015748) - [The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy. Alam F, Gaspari TA, Kemp-Harper BK, et al., Biomedicine and Pharmacotherapy, 2023](https://doi.org/10.1016/j.biopha.2023.114370) - [B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Marshall SA, O'Sullivan K, Ng HH, et al., European Journal of Pharmacology, 2017](https://doi.org/10.1016/j.ejphar.2017.05.005) - [A Lipidated Single-B-Chain Derivative of Relaxin Exhibits Improved In Vitro Serum Stability without Altering Activity. Praveen P, Wang C, Handley TNG, et al., International Journal of Molecular Sciences, 2023](https://doi.org/10.3390/ijms24076616) - [Single chain peptide agonists of relaxin receptors. Praveen P, Kocan M, Valkovic A, Bathgate R, Hossain MA, Molecular and Cellular Endocrinology, 2019](https://doi.org/10.1016/j.mce.2019.01.008) ### Side effects No human safety data; effects unknown beyond animal studies. As a relaxin-family agonist, vasodilation with lowered blood pressure and reflex tachycardia are plausible class effects. Purity and identity of research-grade material is an added practical risk. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: About 6 min in serum in vitro; no in vivo pharmacokinetic study in any species (Praveen 2023) - Molecular weight: 2986.6 Da - Sequence: VIKLSGRELVRAQIAISGMSTWSKRSL-NH2 (27 aa; relaxin-2 B chain 7-33 with Cys11Ser and Cys23Ser, C-terminal amide) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## BPC-157 URL: https://peptidelabs.app/peptides/bpc-157/ Also known as: Body Protection Compound 157, PL 14736, PL-10, Bepecin Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic pentadecapeptide derived from a protective protein found in human gastric juice; accelerates tendon, muscle and gut healing in rodent models. BPC-157 (PL 14736, bepecin) is a synthetic 15-residue peptide whose sequence comes from a fragment of a protein in human gastric juice. The evidence base is almost entirely rodent: transected rat Achilles tendon and medial collateral ligament healed faster by biomechanical, functional and histological measures at 10 mcg/kg or 10 ng/kg intraperitoneally (Staresinic 2003; Cerovecki 2010), and it raises VEGFR2 expression and blood flow recovery in rat hindlimb ischemia (Hsieh 2017). No completed randomized human trial has been published; human data are three uncontrolled pilot reports totalling under 30 subjects (McGuire 2025). FDA placed BPC-157 in category 2 of its 503A compounding interim policy, the significant-safety-risk list; the nomination was later withdrawn by the nominator and the entry now sits in the withdrawn table on the same page. ### Benefits Tendon, ligament and muscle healing in animal models, gastrointestinal mucosal protection, reduced inflammation, neuroprotective and dopamine-system effects in rodents ### Dosing reference - Research dose: 250 to 500 mcg daily: research-community range, no published human dose-finding study. Rodent studies used 10 mcg/kg and 10 ng/kg intraperitoneally - Range: 250 to 500 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Subcutaneous or intramuscular in research use; also active per-orally in rats (0.16 mcg/mL in drinking water healed transected ligament; Cerovecki 2010). Injection near the injury is community practice, not a published comparison. Plasma half-life is under 30 min in rat and dog with linear kinetics, and intramuscular bioavailability is 14 to 19% in rats and 45 to 51% in beagles (He 2022), so the long-lasting effects seen in animals are not explained by exposure. ### Mechanism Proposed mechanisms, all from animal and cell work. BPC-157 increases VEGFR2 expression and promotes its internalization, activating the VEGFR2-Akt-eNOS pathway; blocking endocytosis with dynasore abolished the effect in human endothelial cells, and treated rats recovered hindlimb blood flow faster (Hsieh 2017). In rat Achilles tendon fibroblasts it raised growth hormone receptor mRNA and protein dose-dependently, and added growth hormone then increased proliferation through JAK2 (Chang 2014). It also increased tendon fibroblast outgrowth, survival under oxidative stress and migration, with dose-dependent phosphorylation of FAK and paxillin (Chang 2011). Effects on dopaminergic, serotonergic and GABAergic signaling are reported in rodent behavioral models and are not established in humans. ### Evidence Preclinical: animal or in vitro data only - Transected rat Achilles tendon recovered fully at 10 mcg, 10 ng or 10 pg/kg intraperitoneally daily, with higher load to failure and reestablished tendon integrity by day 14 (Staresinic et al., 2003) - Rat medial collateral ligament healing improved over 90 days whether given intraperitoneally (10 mcg or 10 ng/kg), topically in cream, or per-orally in drinking water at 0.16 mcg/mL (Cerovecki et al., 2010) - Raised growth hormone receptor expression in rat tendon fibroblasts, with growth hormone then increasing proliferation via JAK2 (Chang et al., 2014) - Increased VEGFR2 expression and internalization, activated VEGFR2-Akt-eNOS signaling and accelerated blood flow recovery in rat hindlimb ischemia (Hsieh et al., 2017) - In rats and beagle dogs, plasma half-life was under 30 min with linear kinetics and intramuscular bioavailability of 14 to 19% and 45 to 51% respectively (He et al., 2022) - Human-trial status: no completed randomized trial has been published. Published human exposure is three uncontrolled pilot reports totalling under 30 subjects (intra-articular knee pain, interstitial cystitis, a 2-subject IV safety study); a phase 2 hamstring-strain trial (NCT07437547) and a phase 1 rotator-cuff trial (NCT07803250) are registered and not yet reported ### References - [Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Chang CH, Tsai WC, Hsu YH, Pang JH, Molecules, 2014](https://doi.org/10.3390/molecules191119066) - [The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH, Journal of Applied Physiology, 2011](https://doi.org/10.1152/japplphysiol.00945.2010) - [Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. Staresinic M, Sebecic B, Patrlj L, et al., Journal of Orthopaedic Research, 2003](https://doi.org/10.1016/S0736-0266(03)00110-4) - [Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Cerovecki T, Bojanic I, Brcic L, et al., Journal of Orthopaedic Research, 2010](https://doi.org/10.1002/jor.21107) - [Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. Hsieh MJ, Liu HT, Wang CN, et al., Journal of Molecular Medicine, 2017](https://doi.org/10.1007/s00109-016-1488-y) - [Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs. He L, Feng D, Guo H, et al., Frontiers in Pharmacology, 2022](https://doi.org/10.3389/fphar.2022.1026182) - [Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing. McGuire FP, Martinez R, Lenz A, Skinner L, Cushman DM, Current Reviews in Musculoskeletal Medicine, 2025](https://doi.org/10.1007/s12178-025-09990-7) - [Safety of Intravenous Infusion of BPC157 in Humans: A Pilot Study. Lee E, Burgess K, Alternative Therapies in Health and Medicine, 2025](https://pubmed.ncbi.nlm.nih.gov/40131143/) ### Side effects No controlled human safety trial exists, so long-term risk is unknown. Three uncontrolled human pilot reports (under 30 subjects in total) recorded no adverse effects, including an IV infusion of up to 20 mg in two adults with no change in cardiac, liver, kidney, thyroid or glucose markers (Lee 2025). Commonly reported by users: injection-site irritation, transient nausea, headache. FDA placed BPC-157 in category 2 of the 503A compounding interim policy, citing possible immunogenicity by some routes and difficulty characterizing peptide-related impurities; that nomination was withdrawn and the substance now appears in the withdrawn table of the same FDA page. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Under 30 min (rat and beagle dog, IV and IM; linear kinetics). No human pharmacokinetic study published - Bioavailability: Intramuscular: 14 to 19% (rat), 45 to 51% (beagle dog). Oral: active per-orally in rodents, absolute oral bioavailability not measured in any species - Molecular weight: 1419.53 Da - Sequence: Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val ### Stacks with - [TB-500](https://peptidelabs.app/peptides/tb-500/) - [GHK-Cu](https://peptidelabs.app/peptides/ghk-cu/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## BPC-157 + TB-500 + GHK-Cu (Glow Blend) URL: https://peptidelabs.app/peptides/bpc-157-tb-500-ghk-cu-glow-blend/ Also known as: Glow Stack, Skin Rejuvenation Blend, Triple Healing Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of BPC-157, TB-500 (Ac-LKKTETQ) and GHK-Cu, sold mostly as 70 mg (10/10/50 mg); each component has animal or cell data, and no study has tested the three together. Sold as a 70 mg vial holding 10 mg BPC-157, 10 mg TB-500 and 50 mg GHK-Cu, so GHK-Cu makes up about 70% of each dose. TB-500 is the acetylated fragment Ac-LKKTETQ, not full thymosin beta-4 (Esposito 2012). BPC-157 and TB-500 have rodent tissue-repair data; GHK-Cu raised collagen synthesis in fibroblast culture and rat wounds. GHK-Cu human data are topical only, with a positive diabetic ulcer trial and a negative venous ulcer trial, and no injected human study exists. The one study pairing BPC-157 and TB-500 found no added benefit in rat tendon repair (Biçer 2026). No study has tested the three-peptide blend. FDA lists BPC-157, TB-500 and injectable GHK-Cu on its compounding safety-risk page in the withdrawn-nomination table. ### Benefits Tendon and ligament repair (rodent, BPC-157); angiogenesis and wound repair (rodent and cell, TB-500 fragment); collagen synthesis (cell and rat, GHK-Cu); mixed topical wound results (human, GHK-Cu, not injected). No data for the blend ### Dosing reference - Research dose: 500 to 750 mcg of blend daily (about 70 to 110 mcg each of BPC-157 and TB-500 and 360 to 540 mcg GHK-Cu at the 10/10/50 mg ratio): vendor/community range, no published human dose of the blend - Range: 500 to 750 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 70 mg Subcutaneous in community use. The loading-then-maintenance schedule has no published basis. The numeric range dates from when the catalog listed a 15 mg vial with 5 mg of each peptide; vendors now sell a 70 mg vial at 10/10/50 mg, which changes the per-component amounts above. GHK-Cu human data are topical: a daily gel in diabetic foot ulcers and a 0.4% cream in venous ulcers. ### Mechanism Proposed, from separate component studies; no study has measured an interaction. BPC-157 activated VEGFR2-Akt-eNOS signalling in rat ischemic limbs. TB-500 carries the actin-binding motif of thymosin beta-4, which drove endothelial migration and sprouting (Philp 2003). GHK-Cu raised collagen synthesis in fibroblasts from 10^-12 M, peaking at 10^-9 M (Maquart 1988). The skin 'glow' attributed to the injected blend has not been tested; GHK-Cu skin data come from cell, rodent and topical human work. ### Evidence Preclinical: animal or in vitro data only - Rat Achilles tendon repair (n=32): BPC-157 and TB-500 each improved histology, and the pair gave no added benefit over either alone; GHK-Cu was not tested (Biçer et al., 2026) - BPC-157 at 10 mcg or 10 ng/kg intraperitoneally restored transected rat Achilles tendon integrity and load to failure by day 14 (Staresinic et al., 2003) - GHK-Cu raised collagen synthesis in fibroblast culture from 10^-12 M, peaking at 10^-9 M (Maquart et al., 1988) - Topical GHK-Cu gel improved diabetic foot ulcer closure versus vehicle, median 98.5% vs 60.8% (Mulder et al., 1994), but a 0.4% cream was no better than placebo in venous ulcers, n=86 (Bishop et al., 1992) - Human-trial status: no study has tested the blend as sold. GHK-Cu human trials were topical; no injected human study of any of the three components has been published, and BPC-157 has only uncontrolled pilot reports ### References - [Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Biçer O, Adanir O, Güleryüz Y, Balci EC, et al., Joint Diseases and Related Surgery, 2026](https://doi.org/10.52312/jdrs.2026.2951) - [Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. Staresinic M, Sebecic B, Patrlj L, et al., Journal of Orthopaedic Research, 2003](https://doi.org/10.1016/S0736-0266(03)00110-4) - [Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs. He L, Feng D, Guo H, et al., Frontiers in Pharmacology, 2022](https://doi.org/10.3389/fphar.2022.1026182) - [Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012](https://doi.org/10.1002/dta.1402) - [The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003](https://doi.org/10.1096/fj.03-0121fje) - [Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Maquart FX, Pickart L, Laurent M, et al., FEBS Letters, 1988](https://doi.org/10.1016/0014-5793(88)80509-x) - [Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Mulder GD, Patt LM, Sanders L, et al., Wound Repair and Regeneration, 1994](https://doi.org/10.1046/j.1524-475X.1994.20406.x) - [A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. Bishop JB, Phillips LG, Mustoe TA, et al., Journal of Vascular Surgery, 1992](https://doi.org/10.1067/mva.1992.37086) ### Side effects No human safety study of the blend has been published, and none of the three components has controlled injected human safety data. Commonly reported by users (anecdotal): injection-site stinging, redness and lumps, attributed to GHK-Cu, plus transient fatigue. At 50 of 70 mg, GHK-Cu (about 16% copper by mass) dominates each dose; copper load is a theoretical concern in disorders of copper excretion such as Wilson's disease. Listed on FDA's 503A category 2 (safety concerns) page, withdrawn-nomination table, as of 2026-04-22, for BPC-157, TB-500 and injectable GHK-Cu: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: BPC-157 under 30 min (rat and dog). TB-500 and GHK-Cu: not measured in any species. No human PK for any component - Bioavailability: BPC-157 intramuscular 14 to 19% (rat), 45 to 51% (dog); TB-500 and injected GHK-Cu not measured. No data for the blend ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## BPC-157 + TB-500 + KPV + GHK-Cu (KLOW Blend) URL: https://peptidelabs.app/peptides/bpc-157-tb-500-kpv-ghk-cu-klow-blend/ Also known as: KLOW Healing Blend, Quad Peptide Stack, KLOW Blend Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of BPC-157, TB-500 (Ac-LKKTETQ), KPV and GHK-Cu, sold as 80 mg (10/10/10/50 mg); each component has animal or cell data, and no study has tested the four together. Sold as an 80 mg vial holding 10 mg each of BPC-157, TB-500 and KPV plus 50 mg GHK-Cu, so GHK-Cu is over 60% of each dose. TB-500 is the acetylated fragment Ac-LKKTETQ, not full thymosin beta-4 (Esposito 2012). KPV is the C-terminal tripeptide of alpha-MSH (Lys-Pro-Val); it reduced colitis in mice, mostly when given orally. BPC-157 and TB-500 have rodent tissue-repair data, and GHK-Cu raised collagen in cell and rat wound studies, with human data only for topical use. No human trial exists for KPV, TB-500 or the blend, and the one paired study of BPC-157 and TB-500 found no added benefit in rat tendon repair (Biçer 2026). FDA lists all four components (GHK-Cu for injection) on its compounding safety-risk page in the withdrawn-nomination table. ### Benefits Tendon and ligament repair (rodent, BPC-157); angiogenesis and wound repair (rodent and cell, TB-500 fragment); reduced colitis (mouse, KPV); collagen synthesis (cell and rat, GHK-Cu). No data for the blend ### Dosing reference - Research dose: 500 to 1000 mcg of blend daily (about 60 to 125 mcg each of BPC-157, TB-500 and KPV and 310 to 625 mcg GHK-Cu at the 10/10/10/50 mg ratio): vendor/community range, no published human dose of the blend - Range: 500 to 1000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 80 mg Subcutaneous in community use. The loading-then-maintenance schedule has no published basis. The earlier text gave the dose as 0.5 to 1 mL, which at 80 mg in 2 mL would be 20 to 40 mg of blend, 20 to 80 times the numeric range; the numeric range is kept and the volume wording dropped. KPV animal work used oral drinking water, intraperitoneal 1 mg/kg in mice and topical 1 to 10 mg/mL; GHK-Cu human data are topical. ### Mechanism Proposed, from separate component studies; no study has measured an interaction among the four. BPC-157 activated VEGFR2-Akt-eNOS signalling in rat ischemic limbs. TB-500 carries the actin-binding motif of thymosin beta-4 linked to endothelial migration (Philp 2003). KPV entered intestinal epithelial and T cells through the PepT1 transporter and inhibited NF-kB and MAP kinase signalling at nanomolar levels (Dalmasso 2008); it also worked in MC1 receptor-deficient mice, so the effect is partly independent of MC1R (Kannengiesser 2008). GHK-Cu raised collagen synthesis in fibroblasts (Maquart 1988). Most KPV data used oral or colonic delivery; whether subcutaneous KPV reaches the gut mucosa has not been studied. ### Evidence Preclinical: animal or in vitro data only - Rat Achilles tendon repair (n=32): BPC-157 and TB-500 each improved histology, and the pair gave no added benefit over either alone; KPV and GHK-Cu were not tested (Biçer et al., 2026) - BPC-157 at 10 mcg or 10 ng/kg intraperitoneally restored transected rat Achilles tendon integrity and load to failure by day 14 (Staresinic et al., 2003) - Oral KPV in drinking water reduced DSS- and TNBS-induced colitis in mice, acting through PepT1 uptake and NF-kB inhibition (Dalmasso et al., 2008) - GHK-Cu raised collagen synthesis in fibroblast culture from 10^-12 M, peaking at 10^-9 M (Maquart et al., 1988) - Topical GHK-Cu gel improved diabetic foot ulcer closure versus vehicle in a multicenter evaluator-blinded RCT; this was topical, not injected (Mulder et al., 1994) - Human-trial status: no study has tested the blend as sold. No human trial of KPV or Ac-LKKTETQ has been published, BPC-157 has only uncontrolled pilot reports, and GHK-Cu human data are topical ### References - [Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Biçer O, Adanir O, Güleryüz Y, Balci EC, et al., Joint Diseases and Related Surgery, 2026](https://doi.org/10.52312/jdrs.2026.2951) - [Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. Staresinic M, Sebecic B, Patrlj L, et al., Journal of Orthopaedic Research, 2003](https://doi.org/10.1016/S0736-0266(03)00110-4) - [Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012](https://doi.org/10.1002/dta.1402) - [The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003](https://doi.org/10.1096/fj.03-0121fje) - [PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al., Gastroenterology, 2008](https://doi.org/10.1053/j.gastro.2007.10.026) - [Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Kannengiesser K, Maaser C, Heidemann J, et al., Inflammatory Bowel Diseases, 2008](https://doi.org/10.1002/ibd.20334) - [Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Maquart FX, Pickart L, Laurent M, et al., FEBS Letters, 1988](https://doi.org/10.1016/0014-5793(88)80509-x) - [Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Mulder GD, Patt LM, Sanders L, et al., Wound Repair and Regeneration, 1994](https://doi.org/10.1046/j.1524-475X.1994.20406.x) ### Side effects No human safety study of the blend has been published, and FDA states it has identified no human exposure data for KPV or the LKKTETQ fragment. Commonly reported by users (anecdotal): injection-site stinging, redness and lumps, attributed to GHK-Cu, plus transient fatigue. GHK-Cu is 50 of 80 mg and about 16% copper by mass; copper load is a theoretical concern in disorders of copper excretion such as Wilson's disease. Listed on FDA's 503A category 2 (safety concerns) page, withdrawn-nomination table, as of 2026-04-22, for BPC-157, TB-500, KPV and injectable GHK-Cu: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: BPC-157 under 30 min (rat and dog). TB-500, KPV and GHK-Cu: not measured in any species. No human PK for any component - Bioavailability: BPC-157 intramuscular 14 to 19% (rat), 45 to 51% (dog). KPV active orally in mice via PepT1. TB-500, KPV and GHK-Cu by injection not measured ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## BPC-157 + TB-500 Blend URL: https://peptidelabs.app/peptides/bpc-157-tb-500-blend/ Also known as: Healing Blend, Recovery Stack, BPC/TB Combo Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of BPC-157 and TB-500 (Ac-LKKTETQ), two peptides with rodent tissue-repair data; the one rat study of the pair found no added benefit over either alone. A lyophilized mix of BPC-157 and TB-500, sold as 10 mg (5 mg each) or 20 mg (10 mg each) vials. TB-500 is the acetylated fragment Ac-LKKTETQ, residues 17 to 23 of thymosin beta-4, not the full protein (Esposito 2012). Each component has rodent and cell data on its own: BPC-157 for tendon and ligament healing, TB-500 for angiogenesis and dermal repair. The only study of the pair, a 2026 rat Achilles tendon study (n=32), found both peptides improved tendon histology but the combination gave no benefit over either alone (Biçer 2026). No human trial has tested the blend, and neither component has a completed randomized human trial. FDA lists both on its compounding safety-risk page in the withdrawn-nomination table. ### Benefits Tendon, ligament and gut repair (rodent, BPC-157); angiogenesis and wound repair (rodent and cell, TB-500 fragment); no additive tendon benefit from the pair (rat). No human data for the blend ### Dosing reference - Research dose: 500 to 750 mcg of blend daily (250 to 375 mcg of each peptide at the 1:1 ratio): vendor/community range, no published human dose of the blend or either component - Range: 500 to 750 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg, 20 mg Subcutaneous in community use; injecting near an injury is community practice, not a published comparison. The loading-then-maintenance schedule has no published basis. At the 1:1 ratio the daily blend dose carries far less TB-500 than the community TB-500 range of 2 to 7.5 mg twice weekly. The rat combination study dosed by weight, intraperitoneally: BPC-157 10 mcg/kg/day and TB-500 60 mcg/kg/day for 4 weeks (Biçer 2026). ### Mechanism Proposed, from component studies only; no study has measured how the two interact. BPC-157 raised VEGFR2 expression and activated VEGFR2-Akt-eNOS signalling in rat ischemic limbs (Hsieh 2017). TB-500 carries the actin-binding motif of thymosin beta-4, which was necessary and sufficient for its angiogenic activity in endothelial cells (Philp 2003). A 2024 study found Ac-LKKTETQ broken down quickly in serum and suggested its metabolite Ac-LKKTE carries the wound-healing activity (Rahaman 2024). In the rat tendon study the authors suggested the lack of an additive effect may reflect shared downstream pathways, which they did not test. ### Evidence Preclinical: animal or in vitro data only - Rat Achilles tendon repair (n=32): BPC-157 10 mcg/kg/day and TB-500 60 mcg/kg/day intraperitoneally each improved histology scores, TB-500 also load to failure, and the combination gave no added benefit over either alone (Biçer et al., 2026) - BPC-157 at 10 mcg or 10 ng/kg intraperitoneally restored transected rat Achilles tendon integrity and load to failure by day 14 (Staresinic et al., 2003) - The seven-residue actin-binding motif in TB-500 matched full thymosin beta-4 for endothelial migration and aortic sprouting at about 50 nM (Philp et al., 2003) - BPC-157 had a plasma half-life under 30 min in rats and dogs, with intramuscular bioavailability of 14 to 19% in rats and 45 to 51% in dogs (He et al., 2022) - Human-trial status: no study has tested the blend as sold. BPC-157 has only uncontrolled human pilot reports; no trial of Ac-LKKTETQ has been published, and human data on thymosin beta-4 cover the full protein, a different molecule ### References - [Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Biçer O, Adanir O, Güleryüz Y, Balci EC, et al., Joint Diseases and Related Surgery, 2026](https://doi.org/10.52312/jdrs.2026.2951) - [Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. Staresinic M, Sebecic B, Patrlj L, et al., Journal of Orthopaedic Research, 2003](https://doi.org/10.1016/S0736-0266(03)00110-4) - [Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Cerovecki T, Bojanic I, Brcic L, et al., Journal of Orthopaedic Research, 2010](https://doi.org/10.1002/jor.21107) - [Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs. He L, Feng D, Guo H, et al., Frontiers in Pharmacology, 2022](https://doi.org/10.3389/fphar.2022.1026182) - [Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. Hsieh MJ, Liu HT, Wang CN, et al., Journal of Molecular Medicine, 2017](https://doi.org/10.1007/s00109-016-1488-y) - [Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012](https://doi.org/10.1002/dta.1402) - [The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003](https://doi.org/10.1096/fj.03-0121fje) - [Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. Rahaman KA, Muresan AR, Min H, et al., Journal of Chromatography B, 2024](https://doi.org/10.1016/j.jchromb.2024.124033) ### Side effects No human safety study of the blend or of TB-500 has been published, and BPC-157 has only uncontrolled pilot reports totalling under 30 people with no adverse effects recorded. FDA states it has identified no human exposure data for the LKKTETQ fragment. Listed on FDA's 503A category 2 (safety concerns) page, withdrawn-nomination table, as of 2026-04-22, for both BPC-157 and TB-500: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. Commonly reported by users (anecdotal): injection-site irritation, transient fatigue, head rush. Both components promote angiogenesis in animal models, so use with active or suspected malignancy is a theoretical concern. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: BPC-157 under 30 min (rat and dog, IV and IM). TB-500 (Ac-LKKTETQ) not measured; rapidly metabolized in rat and human serum. No human PK for either - Bioavailability: BPC-157 intramuscular 14 to 19% (rat), 45 to 51% (dog). TB-500 not measured. No data for the blend ### Stacks with - [GHK-Cu](https://peptidelabs.app/peptides/ghk-cu/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## BPC-157 Capsule URL: https://peptidelabs.app/peptides/bpc-157-capsule/ Also known as: BPC-157 Oral, PL 14736, Bepecin, 137525-51-0 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Oral capsule form of the gastric pentadecapeptide BPC-157, studied mainly in rodent models for gastrointestinal mucosal repair and systemic tissue healing. An oral capsule of the same 15-residue peptide as injectable BPC-157 (id 9). Oral activity is supported in rodents, not humans: rats with a transected medial collateral ligament healed as well on BPC-157 in drinking water (0.16 mcg/mL, about 2 mcg/day per rat) as on intraperitoneal injection (Cerovecki 2010). No study in any species has measured absolute oral bioavailability or plasma levels after oral dosing, and the only published pharmacokinetics are IV and IM (He 2022). A 2015 randomized oral phase 1 in healthy volunteers using 1 mg tablets (NCT02637284) has a status of unknown and no posted results. FDA placed BPC-157 in category 2 of its 503A compounding interim policy, the significant-safety-risk list, citing possible immunogenicity and impurity-characterization problems; the nomination was later withdrawn and the entry now sits in the withdrawn table on that page. ### Benefits Gut health, tissue repair, anti-inflammatory ### Dosing reference - Research dose: 250 to 500 mcg daily: research-community range, no published human oral dose-finding study. The one registered oral phase 1 used 1 to 6 mg tablets - Range: 250 to 500 mcg, 1-2x daily Oral capsule. BPC-157 is unusually stable in gastric juice and was active per-orally in rats given 0.16 mcg/mL in drinking water (Cerovecki 2010), but absolute oral bioavailability has not been measured in any species and no human oral pharmacokinetic data are published (Mateescu 2026). Empty-stomach timing is community practice with no published comparison. ### Mechanism Same peptide as injectable BPC-157, so the same proposed mechanisms apply: increased VEGFR2 expression and internalization with VEGFR2-Akt-eNOS activation in endothelial cells and rat hindlimb ischemia (Hsieh 2017), raised growth hormone receptor expression in rat tendon fibroblasts (Chang 2014), and dose-dependent FAK and paxillin phosphorylation with increased fibroblast migration (Chang 2011). For the oral route specifically, the peptide resists gastric degradation and was effective in drinking water in rats, but whether intact peptide reaches the circulation in humans has not been shown; local action on gut epithelium and systemic action are not distinguished by any published study. ### Evidence Preclinical: animal or in vitro data only - Rat medial collateral ligament healing improved over 90 days when BPC-157 was given per-orally in drinking water at 0.16 mcg/mL, matching intraperitoneal dosing (Cerovecki et al., 2010) - BPC-157 is unusually stable in gastric juice and shows activity by oral, parenteral and topical routes, but has no validated formulation and no measured oral bioavailability in any species (Mateescu et al., 2026) - Published pharmacokinetics cover IV and IM routes only: half-life under 30 min in rat and dog, IM bioavailability 14 to 19% and 45 to 51% (He et al., 2022) - Mechanistic work behind the oral and injectable forms is the same rodent and cell literature: VEGFR2-Akt-eNOS activation (Hsieh et al., 2017) and growth hormone receptor upregulation in tendon fibroblasts (Chang et al., 2014) - Human-trial status: none completed. A randomized oral phase 1 in healthy volunteers with 1 mg tablets was registered in 2015 (NCT02637284) and remains status unknown with no posted results; no oral human data have been published ### References - [Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Cerovecki T, Bojanic I, Brcic L, et al., Journal of Orthopaedic Research, 2010](https://doi.org/10.1002/jor.21107) - [Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs. He L, Feng D, Guo H, et al., Frontiers in Pharmacology, 2022](https://doi.org/10.3389/fphar.2022.1026182) - [BPC-157 as an Investigational Peptide Therapeutic: Biopharmaceutical Challenges, Formulation Strategies, and Translational Development Barriers. Mateescu DM, Gavrilescu DM, Constantinescu FE, et al., Pharmaceutics, 2026](https://doi.org/10.3390/pharmaceutics18050625) - [Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Chang CH, Tsai WC, Hsu YH, Pang JH, Molecules, 2014](https://doi.org/10.3390/molecules191119066) - [The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH, Journal of Applied Physiology, 2011](https://doi.org/10.1152/japplphysiol.00945.2010) - [Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. Hsieh MJ, Liu HT, Wang CN, et al., Journal of Molecular Medicine, 2017](https://doi.org/10.1007/s00109-016-1488-y) ### Side effects No controlled human safety data exist for any route, and oral absorption in humans is unproven. Occasional nausea or GI upset is reported by users. FDA placed BPC-157 in category 2 of the 503A compounding interim policy, citing possible immunogenicity by some routes and peptide impurity and characterization problems; that nomination was later withdrawn and the substance now appears in the withdrawn table of the same FDA page. ### Storage - Storage: Room temperature - Lyophilized: 12+ months ### Pharmacology - Half-life: Under 30 min after IV or IM dosing in rat and dog (He 2022). No oral pharmacokinetic data in any species - Bioavailability: Oral: not measured in any species, although per-oral dosing was effective in rats (Cerovecki 2010). IM: 14 to 19% (rat), 45 to 51% (dog) - Molecular weight: 1419.53 Da - Sequence: Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val ### Stacks with - [TB-500](https://peptidelabs.app/peptides/tb-500/) - [GHK-Cu](https://peptidelabs.app/peptides/ghk-cu/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## Bronchogen URL: https://peptidelabs.app/peptides/bronchogen/ Also known as: AEDL, Ala-Glu-Asp-Leu Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide (AEDL) for bronchial tissue; reported to restore bronchial epithelium in a rat NO2 model of COPD and to drive bronchial cell differentiation in vitro. Bronchogen is a synthetic tetrapeptide (AEDL, Ala-Glu-Asp-Leu) from the St. Petersburg Institute of Bioregulation and Gerontology, listed by that group as a bronchoprotector (Khavinson 2022). In rats with COPD modelled by 60 days of intermittent NO2 exposure, a month of treatment reversed goblet cell hyperplasia and squamous metaplasia, restored ciliated cells and raised secretory IgA (Kuzubova 2015). In human embryonic bronchial cell cultures it raised Ki67, Mcl-1 and the differentiation genes NKX2-1, SCGB1A1 and FOXA1, most in late-passage cells (Khavinson 2014). Nearly all work comes from one group. No controlled human trial has been published; a 2020 review from the same group says oral use is effective in COPD but cites no clinical paper. ### Benefits Bronchial epithelium restoration in a rat COPD model (rodent), bronchial epithelial differentiation and proliferation markers (in vitro) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. The rat COPD study gave a one-month course; its abstract does not state the dose (Kuzubova 2015). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed, from cell and biophysical work by the developing group. In bronchial epithelial cultures the peptide raised proliferation (Ki67, Mcl-1) and bronchial differentiation gene expression (NKX2-1, SCGB1A1, SCGB3A2, FOXA1, FOXA2, MUC4, MUC5AC, SFTPA1), and spectroscopy suggested binding in the DNA major groove (Khavinson 2014). Calorimetry showed it raises DNA melting temperature by 3.1 C, binding both strands without base specificity (Monaselidze 2011). Docking predicts uptake through PEPT1 and LAT transporters (Khavinson 2022). Gene regulation by direct DNA binding is the group's hypothesis and has not been tested independently. ### Evidence Preclinical: animal or in vitro data only - In rats with NO2-induced COPD, one month of treatment removed goblet cell hyperplasia, squamous metaplasia and emphysema, restored ciliated cells and raised secretory IgA (Kuzubova et al., 2015) - Expression of the differentiation factors CXCL12 and Hoxa3 rose in aged human bronchial epithelial cultures (Khavinson et al., 2012) - In human embryonic bronchial cell cultures it raised Ki67, Mcl-1, NKX2-1, SCGB1A1 and FOXA1, strongest in late passages (Khavinson et al., 2014) - Raised DNA melting temperature by 3.1 C in calorimetry, binding both strands (Monaselidze et al., 2011) - Human-trial status: no controlled human trial published; reviews from the developing group describe oral use in COPD and chronic bronchitis without citing a clinical paper ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Peptides tissue-specifically stimulate cell differentiation during their aging. Khavinson VKh, Linkova NS, Polyakova VO, Kheifets OV, et al., Bulletin of Experimental Biology and Medicine, 2012](https://doi.org/10.1007/s10517-012-1664-1) - [Peptide regulation of gene expression and protein synthesis in bronchial epithelium. Khavinson VKh, Tendler SM, Vanyushin BF, Kasyanenko NA, et al., Lung, 2014](https://doi.org/10.1007/s00408-014-9620-7) - [Modulating Effect of Peptide Therapy on the Morphofunctional State of Bronchial Epithelium in Rats with Obstructive Lung Pathology. Kuzubova NA, Lebedeva ES, Dvorakovskaya IV, Surkova EA, et al., Bulletin of Experimental Biology and Medicine, 2015](https://doi.org/10.1007/s10517-015-3047-x) - [Effect of the peptide bronchogen (Ala-Asp-Glu-Leu) on DNA thermostability. Monaselidze JR, Khavinson VKh, Gorgoshidze MZ, Khachidze DG, et al., Bulletin of Experimental Biology and Medicine, 2011](https://doi.org/10.1007/s10517-011-1146-x) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species. Docking predicts transport by PEPT1, LAT1 and LAT2 (Khavinson 2022) - Molecular weight: 446.45 Da - Sequence: AEDL (Ala-Glu-Asp-Leu) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Cagrilintide URL: https://peptidelabs.app/peptides/cagrilintide/ Also known as: AM833, NN9838, NN0174-0833 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Long-acting lipidated amylin analog that activates amylin and calcitonin receptors; once-weekly 0.3 to 4.5 mg cut body weight 6.0 to 10.8% at 26 weeks in a phase 2 trial (n=706). Cagrilintide (AM833, NN9838) is a lipidated, long-acting analog of the pancreatic hormone amylin, designed by Novo Nordisk for once-weekly subcutaneous dosing (Kruse 2021). As monotherapy, a 26-week phase 2 trial in 706 adults with overweight or obesity found weight reductions of 6.0 to 10.8% across 0.3 to 4.5 mg weekly, against 3.0% with placebo and 9.0% with liraglutide 3.0 mg (Lau 2021). Most clinical work pairs it with semaglutide 2.4 mg as CagriSema. Phase 3 trials report a 20.4% mean weight reduction at 68 weeks in adults without diabetes (REDEFINE 1) and 13.7% in adults with type 2 diabetes (REDEFINE 2). No cagrilintide product, alone or combined, has an approval listed in Drugs@FDA as of October 2026. ### Benefits Weight loss as monotherapy (human phase 2 RCT), larger weight loss combined with semaglutide (human phase 3 RCT), lower HbA1c with semaglutide in type 2 diabetes (human phase 2 RCT), reduced food intake (mouse) ### Dosing reference - Research dose: 2.4 mg once weekly in phase 3 (alone and with semaglutide 2.4 mg); phase 2 dose-finding tested 0.3 to 4.5 mg once weekly - Range: 300 to 4500 mcg, 1x weekly - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Subcutaneous, once weekly. Phase 2 escalated to the target dose over up to 6 weeks and treated for 26 weeks (Lau 2021). The phase 1b combination study co-escalated cagrilintide and semaglutide every 4 weeks over 16 weeks (Enebo 2021). Phase 3 used 2.4 mg for 68 weeks, alone or with semaglutide 2.4 mg (Garvey 2025). Investigational; not approved. ### Mechanism Cagrilintide is a nonselective agonist of amylin receptors (the calcitonin receptor paired with RAMP1, 2 or 3) and of the calcitonin receptor itself. Across 25 in vitro endpoints its profile differed from both pramlintide and salmon calcitonin (Fletcher 2021). A C20 fatty diacid attached through a gamma-glutamic acid spacer binds albumin and extends the half-life to about a week (Kruse 2021; Enebo 2021). In diet-induced obese mice, weight loss depended on amylin receptors 1 and 3, and treatment activated neurons in the dorsal vagal complex and lateral parabrachial nucleus (Carvas 2025). Brainstem amylin signalling is the proposed route to reduced food intake in humans. ### Evidence Clinical: at least one published human trial or an approved drug - Phase 1b with semaglutide 2.4 mg, 20 weeks (n=96): cagrilintide 1.2 and 2.4 mg gave 15.7% and 17.1% weight loss vs 9.8% with semaglutide plus placebo; half-life 159 to 195 h (Enebo et al., 2021) - Phase 2 monotherapy, 26 weeks (n=706): 0.3 to 4.5 mg weekly reduced body weight 6.0 to 10.8% vs 3.0% with placebo; 4.5 mg exceeded liraglutide 3.0 mg (9.0%) (Lau et al., 2021) - Phase 2 in type 2 diabetes, 32 weeks (n=92): weight change -8.1% with cagrilintide alone and -15.6% with CagriSema; HbA1c -0.9 and -2.2 points (Frias et al., 2023) - Phase 3 REDEFINE 1, 68 weeks (n=3417, no diabetes): CagriSema 2.4/2.4 mg gave -20.4% vs -3.0% with placebo; gastrointestinal events 79.6% vs 39.9% (Garvey et al., 2025) - Phase 3 REDEFINE 2, 68 weeks (n=1206, type 2 diabetes): CagriSema -13.7% vs -3.4% with placebo (Davies et al., 2025) - Human-trial status: phase 3 as a fixed combination with semaglutide (REDEFINE, REIMAGINE programs); no cagrilintide product approved by the FDA in Drugs@FDA as of October 2026 ### References - [Development of Cagrilintide, a Long-Acting Amylin Analogue. Kruse T, Hansen JL, Dahl K, et al., Journal of Medicinal Chemistry, 2021](https://doi.org/10.1021/acs.jmedchem.1c00565) - [AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists. Fletcher MM, Keov P, Truong TT, et al., Journal of Pharmacology and Experimental Therapeutics, 2021](https://doi.org/10.1124/jpet.121.000567) - [Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Enebo LB, Berthelsen KK, Kankam M, et al., The Lancet, 2021](https://doi.org/10.1016/S0140-6736(21)00845-X) - [Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lau DCW, Erichsen L, Francisco AM, et al., The Lancet, 2021](https://doi.org/10.1016/S0140-6736(21)01751-7) - [Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Frias JP, Deenadayalan S, Erichsen L, et al., The Lancet, 2023](https://doi.org/10.1016/S0140-6736(23)01163-7) - [Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT, Blüher M, Osorto Contreras CK, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2502081) - [Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. Davies MJ, Bajaj HS, Broholm C, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2502082) - [Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. Carvas AO, Leuthardt A, Kulka P, et al., EBioMedicine, 2025](https://doi.org/10.1016/j.ebiom.2025.105836) ### Side effects In the phase 2 monotherapy trial, gastrointestinal events (nausea, constipation, diarrhoea) affected 41 to 63% vs 32% on placebo, nausea alone 20 to 47% vs 18%, and administration-site reactions were common; 4% stopped for adverse events (Lau 2021). With semaglutide 2.4 mg, gastrointestinal events affected 79.6% vs 39.9% on placebo over 68 weeks, mostly transient and mild to moderate (Garvey 2025). Safety of cagrilintide alone beyond 68 weeks is not published. ### Storage - Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 24+ months refrigerated - Reconstituted: 28 days refrigerated ### Pharmacology - Half-life: 159 to 195 h (adults with overweight or obesity, subcutaneous, given with semaglutide 2.4 mg); median tmax 24 to 72 h - Bioavailability: No absolute bioavailability published; subcutaneous exposure rose in proportion to dose from 0.16 to 4.5 mg (human, Enebo 2021) - Molecular weight: 4409.1 Da - Sequence: [C20 diacid-gamma-Glu]-KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH2 (Cys2-Cys7 disulfide) ### Stacks with - [Semaglutide](https://peptidelabs.app/peptides/semaglutide/) ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Cardiogen URL: https://peptidelabs.app/peptides/cardiogen/ Also known as: AEDR, Ala-Glu-Asp-Arg Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide (AEDR) for heart tissue; studied in rat myocardial explants and mouse fibroblasts, where it raised proliferation and cytoskeletal proteins. Cardiogen is a synthetic tetrapeptide (AEDR, Ala-Glu-Asp-Arg) from the St. Petersburg Institute of Bioregulation and Gerontology, listed as a cardioprotector; the source cited for that label is a US patent, not a study (Khavinson 2022). Published work is in tissue culture and rats: at 10^-12 M it stimulated proliferation and lowered p53 in myocardial explants from young and old rats (Chalisova 2009), raised actin, tubulin, vimentin and lamins A and C 2 to 5 fold in mouse embryonic fibroblasts (Khavinson 2012), and slowed transplanted M-1 sarcoma growth in old rats through tumor necrosis and apoptosis (Levdik 2009). No study in a heart disease model and no human trial has been published. ### Benefits Myocardial explant cell proliferation and lower p53 (rat tissue culture), cytoskeletal and nuclear matrix protein synthesis (mouse cells in vitro), slowed M-1 sarcoma growth (rat) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. Published work used 10^-12 M in tissue culture (Chalisova 2009); no in vivo dose for a heart indication has been published. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed, from cell culture only. The peptide raised synthesis of cytoskeletal proteins (actin, tubulin, vimentin) and nuclear matrix proteins (lamin A, lamin C) in mouse embryonic fibroblasts, which the authors link to more proliferation and less apoptosis (Khavinson 2012). In rat myocardial explants it lowered p53 expression (Chalisova 2009). Its effect on sarcoma growth appeared to act through tumor blood vessels rather than direct cytotoxicity (Levdik 2009). Gene regulation by direct DNA binding is the developing group's hypothesis, not an established mechanism. ### Evidence Preclinical: animal or in vitro data only - At 10^-12 M, stimulated proliferation and lowered p53 in myocardial explant cultures from 3 and 24 month old rats (Chalisova et al., 2009) - Raised actin, tubulin and vimentin 2 to 5 fold and lamins A and C 2 to 3 fold in mouse embryonic fibroblasts (Khavinson et al., 2012) - Dose-dependently slowed transplanted M-1 sarcoma in old rats via hemorrhagic necrosis and apoptosis, not direct cytostasis (Levdik et al., 2009) - At 0.05 ng/mL, stimulated growth of rat heart explants in organotypic culture, alongside other tissue peptides (Zakutskii et al., 2006) - Human-trial status: no published human study of any design ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Tetrapeptide H-Ala-Glu-Asp-Arg-OH stimulates expression of cytoskeletal and nuclear matrix proteins. Khavinson VKh, Lin'kova NS, Polyakova VO, Kvetnoy IM, et al., Bulletin of Experimental Biology and Medicine, 2012](https://doi.org/10.1007/s10517-012-1766-9) - [The effect of the amino acids and cardiogen on the development of myocard tissue culture from young and old rats (in Russian). Chalisova NI, Lesniak VV, Balykina NA, Urt'eva SA, et al., Advances in Gerontology (Uspekhi Gerontologii), 2009](https://pubmed.ncbi.nlm.nih.gov/20210190/) - [Tumor-modifying effect of cardiogen peptide on M-1 sarcoma in senescent rats. Levdik NV, Knyazkin IV, Bulletin of Experimental Biology and Medicine, 2009](https://doi.org/10.1007/s10517-010-0730-9) - [The tissue-specific effect of synthetic peptides-biologic regulators in organotypic tissues culture in young and old rats (in Russian). Zakutskiĭ AN, Chalisova NI, Ryzhak GA, Aniskina AI, et al., Advances in Gerontology (Uspekhi Gerontologii), 2006](https://pubmed.ncbi.nlm.nih.gov/17152728/) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. The rat sarcoma study reports effects on tumor vasculature that have not been followed up for safety (Levdik 2009). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species. Docking predicts transport by LAT1 and PEPT1 (Khavinson 2022) - Molecular weight: 489.48 Da - Sequence: AEDR (Ala-Glu-Asp-Arg) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Cartalax URL: https://peptidelabs.app/peptides/cartalax/ Also known as: AED, Ala-Glu-Asp, T-31 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tripeptide (AED) for cartilage; in vitro it raised chondrogenic markers in aging human stem cells and reduced senescence markers in chondrocytes. Cartalax is a synthetic tripeptide (AED, Ala-Glu-Asp) from the St. Petersburg Institute of Bioregulation and Gerontology, listed as a chondroprotector; the source cited for that label is a Russian patent (Khavinson 2022). The published work is in cell culture: at 200 ng/mL it raised SOX9, aggrecan, type II collagen and COMP in aging human mesenchymal stem cells (Myakisheva 2023), normalized p16, p21, p53, TNF-alpha and Sirt1 in senescent chondrocytes, and raised sirtuin-1, sirtuin-6 and collagen I in aging skin fibroblasts (Fridman 2020). No animal model of osteoarthritis and no human trial has been published. ### Benefits Chondrogenic gene and protein expression in aging mesenchymal stem cells (in vitro), lower senescence markers in chondrocytes (in vitro), sirtuin and collagen I synthesis in skin fibroblasts (in vitro) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. The only published concentrations are in cell culture (200 ng/mL; Myakisheva 2023). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed, from cell culture only. In aging human mesenchymal stem cells the peptide raised gene expression and synthesis of chondrogenic differentiation proteins (SOX9, aggrecan, collagen II, COMP) (Myakisheva 2023). In chondrocytes with a senescence-associated secretory phenotype it lowered p16, p21, p53, TNF-alpha and IL-1alpha and raised Sirt1. In skin fibroblasts it raised sirtuin-1, sirtuin-6 and collagen I (Fridman 2020) and inhibited MMP-9 and caspase-3 (Lin'kova 2016). MMP inhibition in cartilage itself has not been shown. ### Evidence Preclinical: animal or in vitro data only - At 200 ng/mL, raised SOX9, aggrecan, type II collagen and COMP expression in aging human mesenchymal stem cells (Myakisheva et al., 2023) - Normalized senescence markers (p16, p21, p53, TNF-alpha, IL-1alpha, Sirt1) in aging chondrocyte cultures (Myakisheva et al., 2023) - Raised sirtuin-1, sirtuin-6 and collagen I in human skin fibroblasts during replicative aging (Fridman et al., 2020) - Inhibited MMP-9 and caspase-3 and raised Ki-67 in aging skin fibroblast cultures (Lin'kova et al., 2016) - Human-trial status: no published human study and no animal osteoarthritis model ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [The influence of peptides on the chondrogenic differentiation of human mesenchymal stem cells during replicative aging (in Russian). Myakisheva SN, Linkova NS, Diatlova AS, Polyakova VO, et al., Advances in Gerontology (Uspekhi Gerontologii), 2023](https://pubmed.ncbi.nlm.nih.gov/37782646/) - [Peptides prevent the forming of secretory phenotype of chondrocytes associated with the aging (in Russian). Myakisheva SN, Linkova NS, Kozhevnikova EO, Polyakova VO, et al., Advances in Gerontology (Uspekhi Gerontologii), 2023](https://pubmed.ncbi.nlm.nih.gov/37356100/) - [Comparison of the Effects of KE and AED Peptides on Functional Activity of Human Skin Fibroblasts during Their Replicative Aging. Fridman NV, Linkova NS, Kozhevnikova EO, Gutop EO, et al., Bulletin of Experimental Biology and Medicine, 2020](https://doi.org/10.1007/s10517-020-05022-1) - [Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro. Lin'kova NS, Drobintseva AO, Orlova OA, Kuznetsova EP, et al., Bulletin of Experimental Biology and Medicine, 2016](https://doi.org/10.1007/s10517-016-3370-x) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species - Molecular weight: 333.29 Da - Sequence: AED (Ala-Glu-Asp) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Cerebrolysin URL: https://peptidelabs.app/peptides/cerebrolysin/ Also known as: Brain-derived peptide preparation, FPF 1070 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Porcine brain-derived mixture of low-molecular-weight neuropeptides and free amino acids with neurotrophic activity; trialled in humans for stroke and dementia. Cerebrolysin is a peptide preparation made from porcine brain, a mixture of low-molecular-weight peptides and free amino acids rather than a single compound. Most human research is in stroke. The CASTA randomized trial in Asia was neutral on its primary endpoint, a sponsor-linked meta-analysis of the CARS trials reported better motor recovery, and a 2023 Cochrane review found no effect on mortality with more non-fatal serious adverse events. It is sold in some countries under national authorisation, is not centrally authorised by EMA, and has no US approval. ### Benefits Motor recovery after ischemic stroke (human RCT meta-analysis, sponsor-affiliated), neurotrophic activity (preclinical, proposed) ### Dosing reference - Research dose: 5-10 ml intramuscular 5-10 mL intramuscular injection. 10-20 day cycles. Pre-filled ampules, no reconstitution needed. ### Mechanism Cerebrolysin is a standardized porcine brain extract containing a mixture of low molecular weight neuropeptides (<10 kDa) and free amino acids. The peptide fraction contains neurotrophic factor-like activity similar to BDNF, GDNF, and NGF. Enhances neuroplasticity by promoting dendritic sprouting, synaptogenesis, and neurogenesis. Reduces neuronal apoptosis and oxidative damage. Modulates neurotransmitter systems including cholinergic and glutamatergic pathways. Also has anti-inflammatory effects reducing microglial activation in neuroinflammation. ### Evidence Clinical: at least one published human trial or an approved drug - In the CASTA double-blind placebo-controlled trial in acute ischemic stroke in Asia, the primary endpoint was neutral (Heiss et al., 2012) - A meta-analysis of the CARS trials reported better motor recovery after stroke; the authors include sponsor-affiliated investigators (Guekht et al., 2017) - A 2023 Cochrane review of acute ischaemic stroke trials found no mortality benefit and more non-fatal serious adverse events with Cerebrolysin, RR 2.39 (Ziganshina et al., 2023) - Human-trial status: stroke RCTs exist with mixed results. Not centrally authorised by EMA; marketed under national authorisations in some countries. No US approval: openFDA returns no application ### References - [Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Heiss WD, Brainin M, Bornstein NM, et al., Stroke, 2012](https://doi.org/10.1161/STROKEAHA.111.628537) - [Safety and efficacy of Cerebrolysin in motor function recovery after stroke: a meta-analysis of the CARS trials. Guekht A, Vester J, Heiss WD, et al., Neurological Sciences, 2017](https://doi.org/10.1007/s10072-017-3037-z) - [Cerebrolysin for acute ischaemic stroke. Ziganshina LE, Abakumova T, Nurkhametova D, et al., Cochrane Database of Systematic Reviews, 2023](https://doi.org/10.1002/14651858.CD007026.pub7) ### Side effects In the 2023 Cochrane review of acute ischaemic stroke trials, non-fatal serious adverse events were more frequent with Cerebrolysin than control (RR 2.39), with no mortality benefit (Ziganshina et al., 2023). Made from porcine brain tissue, relevant to hypersensitivity and to dietary or religious restrictions. Commonly reported (clinical use, not verified in this audit): injection-site reactions, dizziness, headache, agitation, rare hypersensitivity, and heat or sweating with rapid injection. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months refrigerated ### Pharmacology - Half-life: Not characterized; a mixture of peptides and amino acids has no single half-life, and no human PK study was found - Bioavailability: Given IV or IM; CNS penetration in humans is not measured ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [Selank](https://peptidelabs.app/peptides/selank/) - [Dihexa](https://peptidelabs.app/peptides/dihexa/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Chonluten URL: https://peptidelabs.app/peptides/chonluten/ Also known as: EDG, Glu-Asp-Gly, T-34 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tripeptide (EDG) assigned to bronchial tissue; in vitro it suppressed LPS-induced TNF release by human monocytes. No controlled human trial. Chonluten is a synthetic tripeptide (EDG, Glu-Asp-Gly) from the St. Petersburg Institute of Bioregulation and Gerontology, assigned to bronchial tissue and also listed as a gastroprotector (Khavinson 2022). The clearest data come from an Italian collaboration: in human THP-1 monocytes it inhibited LPS-induced TNF production and reduced adhesion to activated endothelium (Avolio 2022). A peptide coded T-34, which the group's later reviews identify as EDG, normalized antioxidant and anti-inflammatory protein synthesis in a gastric ulcer model (Khavinson 2012). A 2020 review from the developer says oral EDG helped COPD and chronic bronchitis, but cites only the ulcer paper for it (Khavinson 2020). No controlled human trial has been published. ### Benefits Lower LPS-induced TNF and IL-6 release and less endothelial adhesion by monocytes (in vitro), antioxidant and anti-inflammatory protein normalization in a gastric ulcer model (animal, peptide coded T-34) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. No published abstract states a dose in any species. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed. In THP-1 monocytes the peptide increased tyrosine phosphorylation of mitogen-activated kinases, inhibited LPS-induced TNF and IL-6, and reduced monocyte adhesion to LPS-activated endothelial cells, which the authors describe as TNF tolerance (Avolio 2022). The developer's reviews attribute regulation of c-Fos, HSP70, SOD, COX-2 and TNF-alpha genes to EDG (Khavinson 2020). Docking ranks EDG among the strongest ligands of LAT1, LAT2 and PEPT1 (Khavinson 2022). The old claim of action on type I and II alveolar cells has no published source. ### Evidence Preclinical: animal or in vitro data only - Inhibited LPS-induced TNF production by human THP-1 monocytes and reduced their adhesion to activated endothelium (Avolio et al., 2022) - Peptide T-34, later identified by the group as EDG, normalized antioxidant and anti-inflammatory protein synthesis in a gastric ulcer model (Khavinson et al., 2012) - Docking ranks EDG among the best ligands of the LAT1, LAT2 and PEPT1 transporters (Khavinson et al., 2022) - Human-trial status: no controlled human trial published; a 2020 review from the developer describes oral use in COPD and asthmatic bronchitis without a clinical citation (Khavinson et al., 2020) ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line. Avolio F, Martinotti S, Khavinson VK, Esposito JE, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23073607) - [Peptidergic regulation of expression of genes encoding antioxidant and anti-inflammatory proteins. Khavinson VKh, Lin'kova NS, Dudkov AV, Polyakova VO, et al., Bulletin of Experimental Biology and Medicine, 2012](https://doi.org/10.1007/s10517-012-1590-2) - [Peptides: Prospects for Use in the Treatment of COVID-19. Khavinson V, Linkova N, Dyatlova A, Kuznik B, et al., Molecules, 2020](https://doi.org/10.3390/molecules25194389) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species. Docking predicts transport by LAT1, LAT2 and PEPT1 (Khavinson 2022) - Molecular weight: 319.27 Da - Sequence: EDG (Glu-Asp-Gly) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## CJC-1295 URL: https://peptidelabs.app/peptides/cjc-1295/ Also known as: CJC-1295 DAC, DAC:GRF, CJC-1295 with DAC Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview GHRH(1-29) analog carrying a Drug Affinity Complex that binds serum albumin, extending half-life to about a week and sustaining growth hormone and IGF-1 output. CJC-1295 (ConjuChem) is a tetrasubstituted GHRH(1-29) with a C-terminal lysine carrying a maleimidopropionyl group (the 'Drug Affinity Complex') that bonds to Cys34 of serum albumin after injection, protecting the peptide from dipeptidyl peptidase IV (Jette 2005, rat). In two randomized placebo-controlled trials in healthy adults, single SC doses of 30-60 mcg/kg raised mean GH 2- to 10-fold for 6 or more days and IGF-1 1.5- to 3-fold for 9-11 days, with a half-life of 5.8-8.1 days and no serious adverse reactions; weekly or biweekly dosing kept IGF-1 above baseline for up to 28 days (Teichman 2006). A week after 60-90 mcg/kg, GH pulsatility was preserved with trough GH up 7.5-fold and IGF-1 up 45% (Ionescu 2006). Daily dosing normalized growth in GHRH-knockout mice (Alba 2006). Development stopped after phase 2; not approved anywhere. No body-composition, sleep or recovery trial exists. ### Benefits GH 2-10x and IGF-1 1.5-3x for 6-11 days after one injection (human phase 1/2 RCT), preserved GH pulsatility with 7.5x higher trough GH (human), normalized growth in GHRH-knockout mice ### Dosing reference - Research dose: 30-60 mcg/kg SC weekly or every 2 weeks in phase 1/2 trials (about 2-4 mg for 70 kg); research-community range 1-2 mg weekly - Range: 2000 to 4000 mcg, 1x weekly to every 2 weeks - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Subcutaneous. Trials dosed weekly or every 2 weeks; IGF-1 stayed above baseline for up to 28 days after multiple doses, with a cumulative effect (Teichman 2006). Not interchangeable with 'CJC-1295 no DAC' (Mod GRF 1-29), whose action lasts minutes. Research protocols pair it with a GHRP. ### Mechanism CJC-1295 is [D-Ala2, Gln8, Ala15, Leu27]-GHRH(1-29) extended by a lysine whose side chain carries a 3-maleimidopropionyl group. In vivo the maleimide forms a covalent bond with the free thiol of Cys34 on serum albumin, giving an albumin-peptide conjugate that resists dipeptidyl peptidase IV and persists in plasma beyond 72 h in rats (Jette 2005). The conjugate still activates the pituitary GHRH receptor, so GH secretion is driven continuously. In men this raised trough GH 7.5-fold while leaving pulse frequency and amplitude unchanged, and the IGF-1 rise tracked the trough increase (Ionescu 2006). Human half-life is 5.8-8.1 days (Teichman 2006). ### Evidence Clinical: at least one published human trial or an approved drug - Two randomized placebo-controlled trials in healthy adults: GH 2-10x for 6+ days and IGF-1 1.5-3x for 9-11 days after one SC dose; half-life 5.8-8.1 days; no serious adverse reactions (Teichman et al., 2006) - GH pulsatility preserved one week after 60-90 mcg/kg, trough GH 7.5x, mean GH +46%, IGF-1 +45% in healthy men (Ionescu and Frohman, 2006) - Identified as the best of three albumin-binding GHRH(1-29) maleimide derivatives; 4x GH AUC vs GHRH(1-29) in rats (Jette et al., 2005) - Daily 2 mcg doses normalized body length and weight in GHRH-knockout mice (Alba et al., 2006) - Serum proteomic changes (apoA1, transthyretin isoforms) one week after a single dose in 11 young men (Sackmann-Sala et al., 2009) - Human-trial status: phase 1/2 only; development did not continue; not approved anywhere ### References - [Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA, Journal of Clinical Endocrinology & Metabolism, 2006](https://doi.org/10.1210/jc.2005-1536) - [Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Ionescu M, Frohman LA, Journal of Clinical Endocrinology & Metabolism, 2006](https://doi.org/10.1210/jc.2006-1702) - [Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Jette L, Leger R, Thibaudeau K, et al., Endocrinology, 2005](https://doi.org/10.1210/en.2004-1286) - [Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Alba M, Fintini D, Sagazio A, et al., American Journal of Physiology - Endocrinology and Metabolism, 2006](https://doi.org/10.1152/ajpendo.00201.2006) - [Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ, Growth Hormone & IGF Research, 2009](https://doi.org/10.1016/j.ghir.2009.03.001) ### Side effects In the phase 1/2 trials CJC-1295 was 'safe and relatively well tolerated, particularly at 30 or 60 mcg/kg' with no serious adverse reactions and a cumulative effect after repeated doses (Teichman 2006). Injection-site reactions, flushing, headache, water retention, joint aches, carpal tunnel symptoms and reduced insulin sensitivity are commonly reported (anecdotal) with sustained GH elevation. Regulatory: CJC-1295 is in the 503A withdrawn-nomination table of FDA's compounding safety-risk page, which notes serious adverse events reported with it (increased heart rate, systemic vasodilatory reaction), page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: 5.8-8.1 days (human, SC; Teichman 2006) - Molecular weight: 3647.15 Da - Sequence: Y[D-A]DAIFTQSYRKVLAQLSARKLLQDILSR[K(N-epsilon-3-maleimidopropionyl)][NH2] ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [GHRP-6](https://peptidelabs.app/peptides/ghrp-6/) - [GHRP-2](https://peptidelabs.app/peptides/ghrp-2/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## CJC-1295 + GHRP-2 Blend URL: https://peptidelabs.app/peptides/cjc-1295-ghrp-2-blend/ Also known as: CJC/GHRP-2, Potent GH Stack, Mod GRF 1-29 + GHRP-2, CJC-1295 no DAC + GHRP-2 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of CJC-1295 without DAC (Mod GRF 1-29) and GHRP-2 (pralmorelin), 5 mg each; GHRP-2 raised GH and appetite in human studies, and no study has tested the pair. Vendors in the catalog sell this as CJC-1295 without DAC (Mod GRF 1-29) and GHRP-2, 5 mg each. Mod GRF 1-29 has no published study of its own, and its D-Ala2 substitution only extends the half-time of GHRH(1-29) to about 7 min in men (Soule 1994). GHRP-2 is a synthetic hexapeptide ghrelin-receptor agonist approved in Japan only as a single-dose diagnostic for GH deficiency (Chihara 2007); it sustained GH and IGF-1 over a 30-day infusion in older adults and increased food intake 36% in healthy men. IV GHRP-2 given with GHRH was synergistic in children (Pihoker 1995), the rationale for the pairing, but no study has tested this blend. FDA lists injectable GHRP-2 in category 2 for 503B outsourcing and CJC-1295 in the withdrawn-nomination table of its compounding safety-risk page. ### Benefits GH release (human, GHRP-2); increased food intake (human, GHRP-2 infusion); GH release by Mod GRF 1-29 inferred from related GHRH analogs; body-composition and recovery claims untested for the blend ### Dosing reference - Research dose: 200 to 500 mcg of blend per injection (100 to 250 mcg of each at the 5 mg/5 mg ratio), 1 to 3x daily: vendor/community range, no published human dose of the blend or of Mod GRF 1-29 - Range: 200 to 500 mcg, 1-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Subcutaneous in community use, usually fasted. Human GHRP-2 doses: 1 mcg/kg or 100 mcg IV (diagnostic), 1 mcg/kg/h by continuous SC infusion for 30 days in older adults, and 0.3 to 3 mcg/kg/day SC in GH-deficient children. No human dose of Mod GRF 1-29 has been published. The 5 days on, 2 days off pattern is community convention. ### Mechanism Proposed, from component and class studies. Mod GRF 1-29 is a tetrasubstituted GHRH(1-29) analog acting on the pituitary GHRH receptor; its activity has not been measured directly. GHRP-2 activates the ghrelin receptor (GHS-R1a), raising GH within 60 min, and in swine it also raised ACTH and cortisol where ipamorelin did not (Raun 1998). GHRH-receptor and ghrelin-receptor agonists given together raise GH more than either alone, shown for IV GHRP-2 with GHRH in children (Pihoker 1995). GHRP-2's ghrelin-like action also fits the rise in food intake seen with continuous infusion (Laferrere 2005). ### Evidence Preclinical: animal or in vitro data only - D-Ala2 substitution, one of Mod GRF 1-29's four changes, raised the plasma half-time of GHRH(1-29) from 4.3 to 6.7 min in 10 normal men (Soule et al., 1994) - IV GHRP-2 1 mcg/kg in 10 children gave a predictable GH rise with a plasma half-life of 33 min (Pihoker et al., 1998) - 30-day continuous SC infusion at 1 mcg/kg/h sustained pulsatile GH and raised IGF-1 in 17 older adults (Bowers et al., 2004) - SC GHRP-2 infusion increased ad libitum food intake 36% in 7 healthy men (Laferrere et al., 2005) - Human-trial status: no study has tested the blend as sold, and none has tested Mod GRF 1-29 itself. GHRP-2 is approved in Japan only as a GH-deficiency diagnostic (Chihara et al., 2007); IV GHRP-2 plus GHRH, not Mod GRF 1-29, was synergistic in children (Pihoker et al., 1995) ### References - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Jette L, Leger R, Thibaudeau K, et al., Endocrinology, 2005](https://doi.org/10.1210/en.2004-1286) - [Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children. Pihoker C, Kearns GL, French D, Bowers CY, Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.4.4744) - [Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature. Pihoker C, Middleton R, Reynolds GA, Bowers CY, Badger TM, Journal of Clinical Endocrinology & Metabolism, 1995](https://doi.org/10.1210/jcem.80.10.7559885) - [Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. Bowers CY, Granda R, Mohan S, Kuipers J, Baylink D, Veldhuis JD, Journal of Clinical Endocrinology & Metabolism, 2004](https://doi.org/10.1210/jc.2003-031799) - [Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. Laferrere B, Abraham C, Russell CD, Bowers CY, Journal of Clinical Endocrinology & Metabolism, 2005](https://doi.org/10.1210/jc.2004-1719) - [A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Chihara K, Shimatsu A, Hizuka N, Tanaka T, Seino Y, Kato Y; KP-102 Study Group, European Journal of Endocrinology, 2007](https://doi.org/10.1530/EJE-07-0066) - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) ### Side effects No human safety study of the blend or of Mod GRF 1-29 has been published. A 30-day continuous GHRP-2 infusion kept safety screening tests normal in 17 older adults (Bowers 2004). GHRP-2 raised ACTH and cortisol in swine (Raun 1998) and increased hunger in men. Commonly reported by users (anecdotal): water retention, hunger, tingling in the hands and joint aches. CJC-1295 with DAC, a different product, has a half-life of 5.8 to 8.1 days, so mixing up the two forms changes exposure a great deal. Injectable and nasal GHRP-2 is in category 2 of FDA's 503B interim policy (added 2023-09-29), and CJC-1295 is in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. FDA cites serious adverse events with CJC-1295, including increased heart rate and a systemic vasodilatory reaction. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Mod GRF 1-29 not measured; D-Ala2-GHRH(1-29) ~6.7 min (human, IV). GHRP-2 ~33 min (children, IV bolus). The ~30 min figure for Mod GRF is community lore - Bioavailability: Not measured for Mod GRF 1-29. GHRP-2 raised GH after SC and intranasal dosing in humans; absolute bioavailability not reported. No data for the blend ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## CJC-1295 + GHRP-6 Blend URL: https://peptidelabs.app/peptides/cjc-1295-ghrp-6-blend/ Also known as: CJC/GHRP-6, Appetite GH Stack, Bulking Blend, Mod GRF 1-29 + GHRP-6, CJC-1295 no DAC + GHRP-6 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of CJC-1295 without DAC (Mod GRF 1-29) and GHRP-6, 5 mg each; GHRP-6 raised GH in men and synergized with GHRH, and no study has tested this pair. Vendors in the catalog sell this as CJC-1295 without DAC (Mod GRF 1-29) and GHRP-6, 5 mg each. Mod GRF 1-29 has no published study of its own, and its D-Ala2 substitution only extends the half-time of GHRH(1-29) to about 7 min in men (Soule 1994). GHRP-6, the first synthetic GH-releasing hexapeptide (Bowers 1984), raised GH dose-dependently in normal men and acted synergistically with GHRH(1-44) (Bowers 1990); the GHRH plus GHRP-6 test kept a GH response into very old age (Micic 1998). That synergy is the rationale for the pairing, but no study has tested this blend or Mod GRF 1-29 with GHRP-6. FDA lists GHRP-6 in category 2 for 503B outsourcing and CJC-1295 in the withdrawn-nomination table of its compounding safety-risk page. ### Benefits GH release (human, GHRP-6 IV); synergy of GHRP-6 with native GHRH (human, not with Mod GRF 1-29); appetite increase (anecdotal); body-composition and recovery claims untested for the blend ### Dosing reference - Research dose: 200 to 500 mcg of blend per injection (100 to 250 mcg of each at the 5 mg/5 mg ratio), 1 to 3x daily: vendor/community range, no published human dose of the blend or of Mod GRF 1-29 - Range: 200 to 500 mcg, 1-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Subcutaneous in community use, usually fasted. Human GHRP-6 doses were IV: 0.1 to 1 mcg/kg in GH studies, 90 mcg in the GHRH plus GHRP-6 test, and 100 to 400 mcg/kg in a PK study. No human dose of Mod GRF 1-29 has been published. The 5 days on, 2 days off pattern is community convention. ### Mechanism Proposed, from component and class studies. Mod GRF 1-29 is a tetrasubstituted GHRH(1-29) analog acting on the pituitary GHRH receptor; its activity has not been measured directly. GHRP-6 activates the ghrelin receptor (GHS-R1a), and in men 1 mcg/kg IV also raised prolactin and cortisol about 2-fold (Bowers 1990). Given together, GHRH(1-44) and GHRP-6 produced more GH than either alone in men, which suggests the two receptors act through separate, complementary signals. Claims of cardioprotection rest on a pig infarct model for GHRP-6 alone (Berlanga 2007) and have not been studied for the blend. ### Evidence Preclinical: animal or in vitro data only - D-Ala2 substitution, one of Mod GRF 1-29's four changes, raised the plasma half-time of GHRH(1-29) from 4.3 to 6.7 min in 10 normal men (Soule et al., 1994) - GHRP-6 raised peak GH from 1 to 69 mcg/L at 1 mcg/kg IV and acted synergistically with GHRH in normal men, n=18 (Bowers et al., 1990) - GHRH plus GHRP-6 (90 mcg each, IV) produced a preserved GH response in subjects aged 19 to 96 (Micic et al., 1998) - IV GHRP-6 in nine healthy men: distribution half-life 7.6 min, elimination half-life 2.5 h (Cabrales et al., 2013) - Human-trial status: no study has tested the blend as sold, and none has tested Mod GRF 1-29 itself. The human synergy data used native GHRH, not Mod GRF 1-29, and GHRP-6 is not approved anywhere ### References - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Jette L, Leger R, Thibaudeau K, et al., Endocrinology, 2005](https://doi.org/10.1210/en.2004-1286) - [On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Bowers CY, Momany FA, Reynolds GA, Hong A, Endocrinology, 1984](https://doi.org/10.1210/endo-114-5-1537) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) - [Preserved growth hormone (GH) secretion in aged and very old subjects after testing with the combined stimulus GH-releasing hormone plus GH-releasing hexapeptide-6. Micic D, Popovic V, Doknic M, et al., Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.7.4957) - [Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers. Cabrales A, Gil J, Fernandez E, et al., European Journal of Pharmaceutical Sciences, 2013](https://doi.org/10.1016/j.ejps.2012.10.006) - [Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction. Berlanga J, Cibrian D, Guevara L, et al., Clinical Science (London), 2007](https://doi.org/10.1042/CS20060103) ### Side effects No human safety study of the blend or of Mod GRF 1-29 has been published. GHRP-6 at 1 mcg/kg IV raised prolactin and cortisol about 2-fold in men (Bowers 1990). Commonly reported by users (anecdotal): strong hunger, water retention, lethargy after dosing, tingling in the hands. GHRP-6 is in category 2 of FDA's 503B interim policy (added 2023-09-29), and CJC-1295 is in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. FDA cites serious adverse events with CJC-1295, including increased heart rate and a systemic vasodilatory reaction. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Mod GRF 1-29 not measured; D-Ala2-GHRH(1-29) ~6.7 min (human, IV). GHRP-6 ~2.5 h elimination (human, IV bolus). The ~30 min figure for Mod GRF is community lore - Bioavailability: Not measured by subcutaneous injection for either component; human GHRP-6 data are IV. No data for the blend ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## CJC-1295 + Ipamorelin Blend URL: https://peptidelabs.app/peptides/cjc-1295-ipamorelin-blend/ Also known as: CJC/Ipa, GH Stack, Gold Standard GH Blend, Mod GRF 1-29 + Ipamorelin, CJC-1295 no DAC + Ipamorelin Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of CJC-1295 without DAC (Mod GRF 1-29) and ipamorelin, sold as 10 mg (5 mg each); the two act on separate GH-releasing receptors, and no study has tested the pair. Both catalog vendors sell this as CJC-1295 without DAC, also called Mod GRF 1-29, mixed 5 mg/5 mg with ipamorelin. That is a different molecule from CJC-1295 with DAC, which lasts days; Mod GRF 1-29 has no published study of its own, and its D-Ala2 substitution only extends the half-time of GHRH(1-29) to about 7 min in men (Soule 1994). Ipamorelin released GH without raising cortisol in swine (Raun 1998) and has one human PK study and one negative phase 2 trial in postoperative ileus (Beck 2014). GHRH and GHRP-class peptides act synergistically on GH release in men (Bowers 1990), the rationale for pairing them, but no study has tested this blend. FDA lists ipamorelin in category 2 for 503B outsourcing and CJC-1295 in the withdrawn-nomination table of its compounding safety-risk page. ### Benefits GH pulse after IV ipamorelin (human PK study); GH release by Mod GRF 1-29 inferred from related GHRH analogs; body-composition, sleep and recovery claims untested for the blend or either component ### Dosing reference - Research dose: 200 to 500 mcg of blend per injection (100 to 250 mcg of each at the 5 mg/5 mg ratio), 1 to 3x daily: vendor/community range, no published human dose of the blend or of Mod GRF 1-29 - Range: 200 to 500 mcg, 1-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Subcutaneous in community use, usually fasted or at bedtime; neither timing has been compared in a study of this blend. Human ipamorelin doses were IV and weight-based: 4 to 140 nmol/kg over 15 min (about 3 to 100 mcg/kg) in the PK study and 0.03 mg/kg twice daily in the ileus trial. No human dose of Mod GRF 1-29 has been published. The 5 days on, 2 days off pattern is community convention. ### Mechanism Proposed, from component and class studies. Mod GRF 1-29 is a tetrasubstituted GHRH(1-29) analog that binds the GHRH receptor on pituitary somatotrophs; its D-Ala2 change blocks cleavage between residues 2 and 3 in plasma, but its activity has not been measured directly. Ipamorelin is a pentapeptide agonist of the ghrelin receptor (GHS-R1a); in swine it released GH with GHRP-6-like potency without raising ACTH or cortisol (Raun 1998). In men, GHRH(1-44) given with GHRP-6 produced a GH response larger than either alone (Bowers 1990), which is the basis for pairing the two receptor pathways. The older claims of 2 to 5 times greater GH release and of a 'cleanest' stack have no published source for this blend. ### Evidence Preclinical: animal or in vitro data only - D-Ala2 substitution, one of Mod GRF 1-29's four changes, raised the plasma half-time of GHRH(1-29) from 4.3 to 6.7 min in 10 normal men (Soule et al., 1994) - Ipamorelin released GH with GHRP-6-like potency but without ACTH or cortisol rise in swine (Raun et al., 1998) - IV ipamorelin in 40 healthy men: dose-proportional PK, 2 h terminal half-life, single GH peak at 40 min (Gobburu et al., 1999) - Phase 2 RCT of IV ipamorelin in postoperative ileus (n=114): well tolerated, no efficacy difference from placebo (Beck et al., 2014) - Human-trial status: no study has tested the blend as sold, and none has tested Mod GRF 1-29 itself. GHRH(1-44) plus GHRP-6 was synergistic for GH release in men (Bowers et al., 1990); CJC-1295 with DAC, a different molecule, raised GH and IGF-1 for days in phase 1/2 trials (Teichman et al., 2006) ### References - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [In vitro stability of growth hormone releasing factor (GRF) analogs in porcine plasma. Su CM, Jensen LR, Heimer EP, Felix AM, Pan YC, Mowles TF, Hormone and Metabolic Research, 1991](https://doi.org/10.1055/s-2007-1003601) - [Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Jette L, Leger R, Thibaudeau K, et al., Endocrinology, 2005](https://doi.org/10.1210/en.2004-1286) - [Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA, Journal of Clinical Endocrinology & Metabolism, 2006](https://doi.org/10.1210/jc.2005-1536) - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) - [Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999](https://doi.org/10.1023/a:1018955126402) - [Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014](https://doi.org/10.1007/s00384-014-2030-8) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) ### Side effects No human safety study of the blend or of Mod GRF 1-29 has been published. IV ipamorelin was well tolerated in a 114-patient phase 2 trial (Beck 2014). Commonly reported by users (anecdotal): injection-site reactions, flushing, head rush, water retention and joint aches; reduced insulin sensitivity and carpal tunnel symptoms are reported with sustained GH elevation. Ipamorelin is in category 2 of FDA's 503B interim policy (added 2023-09-29), and ipamorelin and CJC-1295 are in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. FDA cites serious adverse events with CJC-1295, including increased heart rate and a systemic vasodilatory reaction. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Mod GRF 1-29 not measured; D-Ala2-GHRH(1-29) ~6.7 min (human, IV). Ipamorelin ~2 h terminal (human, IV). The ~30 min figure for Mod GRF is community lore - Bioavailability: Not measured for either component by subcutaneous injection; human ipamorelin data are IV. No data for the blend ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## CJC-1295 no DAC (Mod GRF 1-29) URL: https://peptidelabs.app/peptides/cjc-1295-no-dac-mod-grf-1-29/ Also known as: Mod GRF 1-29, Modified GRF, CJC-1295 without DAC, tetrasubstituted GRF(1-29) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Tetrasubstituted GHRH(1-29) analog ([D-Ala2, Gln8, Ala15, Leu27]), the peptide part of CJC-1295 without its albumin-binding linker; no published study of this exact peptide, each substitution characterized separately. 'Mod GRF 1-29' is a community name for [D-Ala2, Gln8, Ala15, Leu27]-GHRH(1-29)-NH2, the GHRH portion of CJC-1295 without its C-terminal maleimide-lysine linker (Jette 2005). 'CJC-1295 no DAC' is a vendor coinage. No peer-reviewed study of this exact peptide was found. The substitutions are each characterized separately: D-Ala2 blocks dipeptidyl peptidase IV cleavage between residues 2 and 3 (Su 1991, porcine plasma) and raised the plasma half-time of GHRH(1-29) from 4.3 to 6.7 min in men (Soule 1994); Ala15 raises GHRH-receptor affinity 4-5 fold in vitro (Campbell 1991); replacing Asn8 removes the main deamidation site that degrades GHRH analogs in solution (Friedman 1991); Leu27 replaces oxidation-prone Met27. Human data on the related peptide come only from the DAC conjugate (Teichman 2006). Evidence level is preclinical. ### Benefits GH release expected from GHRH(1-29) pharmacology (no study of the exact peptide), DPP-IV resistance from D-Ala2 (porcine plasma; human PK of D-Ala2-GHRH(1-29)), higher receptor affinity from Ala15 (in vitro), reduced Asn8 deamidation from Gln8 (in vitro) ### Dosing reference - Research dose: No human data for this peptide; research-community range 100-300 mcg SC per injection, 1-3x daily - Range: 100 to 300 mcg, 1-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Subcutaneous in research use. The D-Ala2 substitution extends the plasma half-time of GHRH(1-29) only to about 7 min in men (Soule 1994), so each injection produces a single short GH pulse. GHRH plus GHRP synergy is documented in men for GHRH(1-44) with GHRP-6 (Bowers 1990), not for this peptide specifically. ### Mechanism Acts at the pituitary GHRH receptor like the parent GHRH(1-29). The four substitutions address GHRH's instability: D-Ala2 prevents dipeptidyl peptidase IV from removing the N-terminal dipeptide, the step that inactivates GHRH within minutes (Su 1991); Gln8 removes the asparagine whose deamidation degrades GHRH analogs in neutral solution (Friedman 1991); Ala15 increases receptor affinity by stabilizing the amphiphilic helix (Campbell 1991); Leu27 replaces an oxidizable methionine. In CJC-1295 this same peptide, with a linker added, activates the GHRH receptor while albumin-bound (Jette 2005). Synergy with GHRPs, which act through GHS-R1a, is documented for GHRH itself (Bowers 1990); the '2-3x' figure in the old record had no source. ### Evidence Preclinical: animal or in vitro data only - No peer-reviewed study of this exact peptide was located (PubMed and Crossref searched October 2026) - D-Ala2 substitution reduced metabolic clearance of GHRH(1-29) and raised its plasma half-time from 4.3 to 6.7 min in 10 normal men (Soule et al., 1994) - D-Ala2 completely prevented cleavage between residues 2 and 3 in porcine plasma; Ala15 alone gave a small gain (Su et al., 1991) - Ala15-substituted GHRH(1-29) analogs bound the GHRH receptor 4-5x more tightly in vitro (Campbell et al., 1991) - The same tetrasubstituted peptide plus a maleimide-lysine linker is CJC-1295, which raised GH and IGF-1 for days in humans (Jette et al., 2005; Teichman et al., 2006) - Human-trial status: none for this peptide; evidence is in vitro and animal work on the individual substitutions ### References - [Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Jette L, Leger R, Thibaudeau K, et al., Endocrinology, 2005](https://doi.org/10.1210/en.2004-1286) - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [GRF analogs and fragments: correlation between receptor binding, activity and structure. Campbell RM, Lee Y, Rivier J, Heimer EP, Felix AM, Mowles TF, Peptides, 1991](https://doi.org/10.1016/0196-9781(91)90103-v) - [In vitro stability of growth hormone releasing factor (GRF) analogs in porcine plasma. Su CM, Jensen LR, Heimer EP, Felix AM, Pan YC, Mowles TF, Hormone and Metabolic Research, 1991](https://doi.org/10.1055/s-2007-1003601) - [Degradation of growth hormone releasing factor analogs in neutral aqueous solution is related to deamidation of asparagine residues. Replacement of asparagine residues by serine stabilizes. Friedman AR, Ichhpurani AK, Brown DM, et al., International Journal of Peptide and Protein Research, 1991](https://doi.org/10.1111/j.1399-3011.1991.tb00727.x) - [Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA, Journal of Clinical Endocrinology & Metabolism, 2006](https://doi.org/10.1210/jc.2005-1536) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) - [Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. Prakash A, Goa KL, BioDrugs, 1999](https://doi.org/10.2165/00063030-199912020-00007) ### Side effects No safety data exist for this exact peptide. For GHRH(1-29) itself, transient facial flushing and injection-site pain were the common trial adverse events (Prakash 1999). Head rush, water retention, joint aches and reduced insulin sensitivity are commonly reported (anecdotal). ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not reported for this exact peptide; D-Ala2-GHRH(1-29) ~6.7 min (human, IV infusion; Soule 1994). The ~30 min figure is community lore - Molecular weight: 3367.9 Da - Sequence: Y[D-A]DAIFTQSYRKVLAQLSARKLLQDILSR[NH2] ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [GHRP-6](https://peptidelabs.app/peptides/ghrp-6/) - [GHRP-2](https://peptidelabs.app/peptides/ghrp-2/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## Cortagen URL: https://peptidelabs.app/peptides/cortagen/ Also known as: Korthagen, AEDP, Ala-Glu-Asp-Pro Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide (AEDP) designed from the brain extract Cortexin; studied in rats for sciatic nerve regeneration and in rodent brain for antioxidant effects. Cortagen (also spelled Korthagen) is a synthetic tetrapeptide (AEDP, Ala-Glu-Asp-Pro) made by the St. Petersburg Institute of Bioregulation and Gerontology from the amino acid make-up of Cortexin, a brain cortex peptide drug (Anisimov 2004). In rats with a cut and sutured sciatic nerve, 10 mcg/kg intramuscularly for 10 days raised regrowth rate by 27% and conduction velocity by 40% (Turchaninova 2000). It lowered lipid peroxidation in rat brain and serum (Kozina 2007) and sped recovery of behavior in rats with chronic brain ischemia (Zarubina 2011). One paper says it aided human nerve recovery, but no human study is indexed. ### Benefits Faster sciatic nerve fiber regrowth and conduction (rat), lower lipid peroxidation in brain and serum (rat), gene expression changes in heart (mouse) ### Dosing reference - Research dose: 200 to 1000 mcg daily in 10 to 20 day courses: vendor/community range, no published human dose. Rats received 10 mcg/kg intramuscularly - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. The nerve study gave 10 mcg/kg intramuscularly daily for 10 days in rats (Turchaninova 2000). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed. In mouse heart, five daily injections changed expression of 110 known genes out of 15,247 transcripts screened (up to 5.4 fold up, 2.9 fold down) (Anisimov 2004). In rats it lowered lipid peroxidation products and oxidative protein modification in serum and cortex (Kozina 2007). Blood-brain barrier passage has not been measured; the old claim that it enters neurons and regulates synaptic genes has no published source. ### Evidence Preclinical: animal or in vitro data only - At 10 mcg/kg intramuscularly for 10 days after sciatic nerve transection, nerve fiber growth rate rose 27% and conduction velocity 40% in rats (Turchaninova et al., 2000) - Five daily injections changed expression of 110 known genes in mouse heart by cDNA microarray (Anisimov et al., 2004) - Lowered lipid peroxidation products and oxidative protein modification in rat serum and cerebral cortex (Kozina et al., 2007) - Sped recovery of behavior and limited lipid peroxidation in rats with chronic brain ischemia (Zarubina et al., 2011) - Human-trial status: no indexed human study; a 2004 paper states it aided human peripheral nerve recovery without giving data ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray. Anisimov SV, Khavinson VKh, Anisimov VN, Neuro Endocrinology Letters, 2004](https://pubmed.ncbi.nlm.nih.gov/15159690/) - [Effect of tetrapeptide cortagen on regeneration of sciatic nerve. Turchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, et al., Bulletin of Experimental Biology and Medicine, 2000](https://pubmed.ncbi.nlm.nih.gov/11276314/) - [Effects of bioactive tetrapeptides on free-radical processes. Kozina LS, Bulletin of Experimental Biology and Medicine, 2007](https://doi.org/10.1007/s10517-007-0230-8) - [Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia (in Russian). Zarubina IV, Shabanov PD, Eksperimental'naia i Klinicheskaia Farmakologiia, 2011](https://pubmed.ncbi.nlm.nih.gov/21476278/) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species; brain penetration not tested - Molecular weight: 430.41 Da - Sequence: AEDP (Ala-Glu-Asp-Pro) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Decapeptide-12 URL: https://peptidelabs.app/peptides/decapeptide-12/ Also known as: Lumixyl, Lumixyl peptide, YRSRKYSSWY Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic decapeptide (YRSRKYSSWY, Lumixyl) that competitively inhibits tyrosinase in vitro; a 5-person split-face placebo-controlled pilot and open-label studies report lighter melasma. Decapeptide-12 came from an oligopeptide library screened by Hantash's group for tyrosinase inhibitors that are not toxic to melanocytes; the 10-residue hit inhibited mushroom tyrosinase with an IC50 of 40 microM (hydroquinone 680 microM) and cut melanocyte melanin 43% over 7 days (Abu Ubeid et al., 2009). It is sold as Lumixyl. Human data: a split-face, double-blind, placebo-controlled pilot in five women with melasma at 0.01% twice daily for 16 weeks (Hantash and Jimenez, 2009), then open-label studies of a regimen pairing it with 20% glycolic acid and sunscreen (Kassim et al., 2012; Ramírez et al., 2013). Most studies come from the developer. ### Benefits Melasma lightening (split-face RCT, n=5; open-label, n=33), photodamage pigment clearance (open-label, n=13), tyrosinase inhibition and lower melanocyte melanin (in vitro) ### Dosing reference - Research dose: Topical, 0.01% (w/w) cream in all published human studies. No oral or injectable dose exists. Topical cream applied to pigmented areas. Studies ran 16 to 24 weeks; most paired it with glycolic acid and sunscreen, so effects of the peptide alone come only from the five-person pilot. ### Mechanism Competitive inhibition of tyrosinase. In kinetic studies the decapeptide competitively inhibited mushroom tyrosinase (IC50 40 microM) and at 100 microM inhibited human tyrosinase by 25 to 35%, with substrate-dependent results suggesting two catalytic sites. Melanin in cultured human melanocytes fell 43% after 7 days without effects on proliferation or viability (Abu Ubeid et al., 2009). Claims of action at multiple steps of melanogenesis or superiority to hydroquinone in people have no published head-to-head data. ### Evidence Clinical: at least one published human trial or an approved drug - Inhibited mushroom tyrosinase (IC50 40 microM vs 680 microM for hydroquinone) and lowered melanocyte melanin 43% without cytotoxicity (Abu Ubeid et al., 2009) - Split-face, double-blind, placebo-controlled pilot: 0.01% twice daily for 16 weeks in five women with recalcitrant melasma, all improved, no irritation (Hantash and Jimenez, 2009) - Open-label, 33 Hispanic women: a 0.01% cream plus 20% glycolic acid and sunscreen lowered MASI scores 60% by week 16 (Ramírez et al., 2013) - Open-label, 13 women with photodamage pigment: 38.5% reached complete clearance at 24 weeks on the same regimen (Kassim et al., 2012) - Human-trial status: one randomized placebo-controlled pilot (n=5); other studies are open-label multi-product regimens, mostly from the developer's group ### References - [Short-sequence oligopeptides with inhibitory activity against mushroom and human tyrosinase. Abu Ubeid A, Zhao L, Wang Y, Hantash BM, The Journal of investigative dermatology, 2009](https://doi.org/10.1038/jid.2009.124) - [A split-face, double-blind, randomized and placebo-controlled pilot evaluation of a novel oligopeptide for the treatment of recalcitrant melasma. Hantash BM, Jimenez F, Journal of drugs in dermatology : JDD, 2009](https://pubmed.ncbi.nlm.nih.gov/19663110/) - [Treatment of mild to moderate facial melasma with the Lumixyl topical brightening system. Hantash BM, Jimenez F, Journal of drugs in dermatology : JDD, 2012](https://pubmed.ncbi.nlm.nih.gov/22527440/) - [Open-label evaluation of the skin-brightening efficacy of a skin-brightening system using decapeptide-12. Kassim AT, Hussain M, Goldberg DJ, Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology, 2012](https://doi.org/10.3109/14764172.2012.672745) - [Open-label evaluation of a novel skin brightening system containing 0.01% decapeptide-12 in combination with 20% buffered glycolic acid for the treatment of mild to moderate facial melasma. Ramírez SP, Carvajal AC, Salazar JC, Arroyave G, et al., Journal of drugs in dermatology : JDD, 2013](https://pubmed.ncbi.nlm.nih.gov/23839199/) - [Combined topical delivery and dermalinfusion of decapeptide-12 accelerates resolution of post-inflammatory hyperpigmentation in skin of color. Bhatia A, Hsu JTs, Hantash BM, Journal of drugs in dermatology : JDD, 2014](https://pubmed.ncbi.nlm.nih.gov/24385124/) ### Side effects No irritation or allergy in the five-person RCT (Hantash and Jimenez, 2009) and no adverse events in the 33-person open-label study (Ramírez et al., 2013). No cytotoxicity to cultured melanocytes at 100 microM (Abu Ubeid et al., 2009). Commonly reported (anecdotal): dryness or redness, mostly attributed to the glycolic acid in combined regimens. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species; skin penetration of decapeptide-12 has not been published - Molecular weight: 1395.54 Da - Sequence: YRSRKYSSWY (Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr) ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Dihexa URL: https://peptidelabs.app/peptides/dihexa/ Also known as: PNB-0408 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Angiotensin IV-derived peptide analog; rodent studies report memory rescue in some models, but the founding papers for its HGF/c-Met mechanism were retracted in 2025. Dihexa is a small modified peptide derived from angiotensin IV, developed as a procognitive agent. Two of the developer group's foundational papers, which proposed HGF/c-Met activation and synaptogenesis, were retracted in April 2025, and a third (McCoy 2013) has carried an expression of concern since 2021. Independent rodent studies are mixed: memory rescue in APP/PS1 mice and after repeated mild brain injury, no protection in a rat Huntington-like model. There are no human trials. Its clinical successor, fosgonimeton, failed a phase 2/3 Alzheimer's trial. ### Benefits Memory rescue in some rodent models (mixed results; one rat model showed no protection) ### Dosing reference - Research dose: 10-30 mcg daily (oral) - no established human dose - Range: 10 to 30 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg, 20 mg No published human dose. Earlier potency claims trace to papers retracted in 2025. ### Mechanism Proposed. The HGF/c-Met mechanism and the claim of potency about 10 million times that of BDNF come from papers retracted in April 2025 (notices PMID 40312092 and 40312093) and are not treated as established. McCoy et al., 2013 described dihexa as a metabolically stabilized angiotensin IV analog; that paper has an expression of concern. Independent work reported memory rescue in APP/PS1 mice with PI3K/AKT pathway changes (Sun et al., 2021) and rescue of working memory after repeated mild traumatic brain injury in rodents (Martino et al., 2025). ### Evidence Preclinical: animal or in vitro data only - Metabolically stabilized angiotensin IV analogs including dihexa were procognitive in rodent dementia models (McCoy et al., 2013); the paper has carried an expression of concern since 2021 - Dihexa rescued cognitive impairment in APP/PS1 mice, with PI3K/AKT signalling changes (Sun et al., 2021) - Dihexa did not protect against 3-nitropropionic acid-induced Huntington-like symptoms in rats (Wells et al., 2024) - An HGF/MET activator rescued working memory deficits after repeated mild traumatic brain injury in rodents (Martino et al., 2025) - Two foundational papers from the developer group were retracted in April 2025 (notices PMID 40312092 and 40312093) - Human-trial status: none for dihexa. Its successor compound fosgonimeton failed the LIFT-AD phase 2/3 trial in mild-to-moderate Alzheimer's disease, NCT04488419 (Porsteinsson et al., 2025) ### References - [Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. McCoy AT, Benoist CC, Wright JW, et al., The Journal of Pharmacology and Experimental Therapeutics, 2013](https://doi.org/10.1124/jpet.112.199497) - [AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Sun X, Deng Y, Fu X, et al., Brain Sciences, 2021](https://doi.org/10.3390/brainsci11111487) - [Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats. Wells RG, Azzam AF, Hiller AL, et al., Journal of Huntington's Disease, 2024](https://doi.org/10.3233/JHD-231507) - [Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury. Martino KA, Nakhre A, Demarest RM, et al., Neurotrauma Reports, 2025](https://doi.org/10.1177/2689288X251392851) - [Fosgonimeton in mild-to-moderate Alzheimer's disease. Porsteinsson AP, Sabbagh M, Tariot PN, et al., Journal of Alzheimer's Disease Reports, 2025](https://doi.org/10.1177/25424823251405817) - [Retraction notice to "Development of Angiotensin IV Analogs as Hepatocyte Growth Factor/Met Modifiers" [J Pharmacol Exp Ther 340 (2012) 539-548. Kawas LH, McCoy AT, Yamamoto BJ, et al., The Journal of Pharmacology and Experimental Therapeutics, 2025](https://doi.org/10.1016/j.jpet.2025.103566) - [Retraction notice to "The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System" [J Pharmacol Exp Ther 351 (2014) 390-402. Benoist CC, Kawas LH, Zhu M, et al., The Journal of Pharmacology and Experimental Therapeutics, 2025](https://doi.org/10.1016/j.jpet.2025.103567) ### Side effects No human safety data. The proposed mechanism is HGF/c-Met activation, a pathway linked to tumor growth, so a theoretical concern about existing tumors has been raised; the papers that established that mechanism are retracted. Commonly reported (anecdotal): headache, irritability. ### Storage - Storage: Room temperature, away from light - Lyophilized: 12+ months - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not established in humans; no half-life verified from non-retracted sources - Bioavailability: Not measured in humans. Oral and subcutaneous activity claims come from the original developer group, whose foundational papers were retracted - Molecular weight: 504.7 Da - Sequence: N-hexanoyl-Tyr-Ile-(6)-aminohexanoic amide (modified dipeptide) ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [Selank](https://peptidelabs.app/peptides/selank/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## DSIP URL: https://peptidelabs.app/peptides/dsip/ Also known as: Delta sleep-inducing peptide, Deltaran (Russian preparation) Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Endogenous nonapeptide first isolated from rabbit brain; older, small human studies looked at sleep onset, stress-axis normalization and chronic pain. DSIP is a nonapeptide isolated in 1977 from rabbit cerebral venous blood, named for the delta electroencephalogram enhancement it produced on intraventricular infusion (Schoenenberger and Monnier, 1977). Human work is small, intravenous and four decades old: double-blind studies in chronic insomniacs reported sleep normalisation and better daytime performance (Schneider-Helmert, 1986), while a controlled parallel-group trial found the effects weak and concluded short-term treatment was unlikely to help much (Bes et al., 1992). An open pilot reported lower pain scores in 7 patients with chronic pain (Larbig et al., 1984). No DSIP gene, precursor or receptor has been identified, and a review by researchers in the field treats the sleep hypothesis as unresolved (Kovalzon and Strekalova, 2006). Measured half-life is minutes. ### Benefits Improved sleep quality, stress reduction, recovery ### Dosing reference - Research dose: 100 to 200 mcg before sleep (community range; human trials used 25 to 30 nmol/kg intravenously, about 1.5 to 2 mg for a 70 kg adult) - Range: 100 to 200 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Human studies used intravenous dosing only: 25 nmol/kg before three nights (Bes et al., 1992) and 30 nmol/kg for 6 doses over a week (Schneider-Helmert, 1986), with slow injection described as necessary (Schneider-Helmert and Schoenenberger, 1983). Those doses are about 1.5 to 2 mg for a 70 kg adult, roughly ten times the 100 to 200 mcg subcutaneous range used in the research community, which no study has tested. Measured half-life is minutes in dog, monkey and rat, and the peptide is degraded in blood (Kato et al., 1984). One small study used the intranasal route (PMID 11763019). ### Mechanism DSIP is the nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, isolated in 1977 from cerebral venous blood of rabbits whose electroencephalogram showed delta enhancement after intraventricular infusion (Schoenenberger and Monnier, 1977). No DSIP gene, precursor protein or receptor has ever been identified, which is why its own reviewers call the sleep-factor hypothesis poorly documented and propose that the activity belongs to an unidentified DSIP-like peptide (Kovalzon and Strekalova, 2006). Reported actions in rodents include effects on glutamate and GABA receptor currents in cortex, hippocampus and cerebellum, and anticonvulsant activity. Blood-brain barrier passage has been measured in guinea pig and dog preparations. The peptide is degraded rapidly in blood, with tryptophan-containing fragments appearing within minutes. ### Evidence Clinical: at least one published human trial or an approved drug - Isolated from rabbit cerebral venous blood; intraventricular infusion enhanced delta and spindle electroencephalogram patterns in 58 rabbits, and five fragments and two analogs did not (Schoenenberger and Monnier, 1977) - Five double-blind human studies with single and repeated intravenous dosing reported sleep normalisation in insomniacs plus higher daytime alertness; slow injection was described as essential (Schneider-Helmert and Schoenenberger, 1983) - One week of intravenous dosing in 18 chronic insomniacs (6 doses at 30 nmol/kg) improved sleep toward normal values, with the effect tracking baseline severity (Schneider-Helmert, 1986) - A double-blind parallel-group trial in 16 chronic insomniacs (25 nmol/kg intravenously before three nights) found higher sleep efficiency and shorter latency, but the authors judged the effects weak and partly attributable to a shift in the placebo group (Bes et al., 1992) - An open pilot in 7 patients with chronic pain episodes reported lower pain scores after intravenous dosing on 5 consecutive days then every 48 to 72 hours (Larbig et al., 1984) - Human-trial status: the human work is small, 1980s and intravenous, with one controlled trial reporting little therapeutic benefit. No modern trial, no approval anywhere, and the field's own review calls the link between DSIP and sleep unresolved (Kovalzon and Strekalova, 2006) ### References - [Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Schoenenberger GA, Monnier M, Proceedings of the National Academy of Sciences, 1977](https://doi.org/10.1073/pnas.74.3.1282) - [Delta-sleep-inducing peptide (DSIP): a review. Graf MV, Kastin AJ, Neuroscience and Biobehavioral Reviews, 1984](https://doi.org/10.1016/0149-7634(84)90022-8) - [Effects of DSIP in man. Multifunctional psychophysiological properties besides induction of natural sleep. Schneider-Helmert D, Schoenenberger GA, Neuropsychobiology, 1983](https://doi.org/10.1159/000117964) - [Efficacy of DSIP to normalize sleep in middle-aged and elderly chronic insomniacs. Schneider-Helmert D, European Neurology, 1986](https://doi.org/10.1159/000116050) - [Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study. Bes F, Hofman W, Schuur J, Van Boxtel C, Neuropsychobiology, 1992](https://doi.org/10.1159/000118919) - [Development of an enzyme immunoassay for delta sleep-inducing peptide (DSIP) and its use in the determination of the metabolic clearance rate of DSIP administered to dogs. Kato N, Honda Y, Ebihara S, Naruse H, Takahashi Y, Neuroendocrinology, 1984](https://doi.org/10.1159/000123952) - [Delta sleep-inducing peptide (DSIP): a still unresolved riddle. Kovalzon VM, Strekalova TV, Journal of Neurochemistry, 2006](https://doi.org/10.1111/j.1471-4159.2006.03693.x) - [Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study. Larbig W, Gerber WD, Kluck M, Schoenenberger GA, European Neurology, 1984](https://doi.org/10.1159/000115716) ### Side effects Reported effects are limited to injection-site irritation, headache, and next-day grogginess. Human data comes from a handful of small studies, so the safety profile is not well characterized. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~4.0 min (dog, IV; clearance 30.7 mL/kg/min), 2.9 min in a monkey and ~2.0 min in rats (Kato et al., 1984); no human figure published - Bioavailability: No bioavailability figure published for any route. Blood-brain barrier passage was measured in perfused guinea pig brain and in dog cerebrospinal fluid; intravenous peptide is degraded in blood within minutes (Kato et al., 1984). - Molecular weight: 848.81 Da - Sequence: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu ### Stacks with - [Epithalon](https://peptidelabs.app/peptides/epithalon/) ### Categories - [Sleep](https://peptidelabs.app/peptides/category/sleep/) ## Epithalon URL: https://peptidelabs.app/peptides/epithalon/ Also known as: Epitalon, Epithalone, AEDG peptide, Ala-Glu-Asp-Gly Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic tetrapeptide Ala-Glu-Asp-Gly (PubChem CID 219042); human cell cultures show telomerase induction, and in mice it raised maximum but not mean lifespan. Epitalon (AEDG) is a synthetic tetrapeptide designed from the amino acid composition of Epithalamin, a bovine pineal gland extract, and later reported in pineal polypeptide complex. The headline findings are in cell culture: added to telomerase-negative human fetal fibroblasts it induced hTERT expression, telomerase activity and telomere elongation (Khavinson 2003), and senescing fibroblasts made about 10 extra passages past the Hayflick limit (Khavinson 2004). An independent 2025 group reproduced dose-dependent telomere lengthening in normal human cells and found ALT activation in cancer lines (Al-Dulaimi 2025). In mice given 1 mcg per animal on 5 days a month for life, mean lifespan did not change (Anisimov 2003). No controlled trial of the synthetic peptide has been published; the long-term human studies used the bovine extract. ### Benefits Telomerase induction and telomere elongation (human fibroblasts in vitro), extra population doublings in senescing human cells (in vitro), raised maximum lifespan and 6-fold fewer leukemias (mouse), melatonin rhythm normalization (reported for the bovine pineal extract, not the peptide) ### Dosing reference - Research dose: 5 to 10 mg daily for 10 to 20 days: research-community range, no published human dose-finding study - Range: 5000 to 10000 mcg, Daily (10-20 day cycle) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg, 50 mg Subcutaneous or intramuscular in research use; intranasal and intramuscular routes were both used in rodent studies. Cycling of 10 to 20 days, 2 to 3 times a year, is community convention with no published basis. Mouse geroprotection studies used 1 mcg per animal, roughly 30 to 40 mcg/kg, on 5 consecutive days each month for life (Anisimov 2003), which is a different schedule from any human protocol. ### Mechanism Proposed mechanisms, all from cell culture and rodent work. In telomerase-negative human fibroblasts AEDG induced expression of the telomerase catalytic subunit and measurable telomerase activity, with telomere elongation (Khavinson 2003); a 2025 independent replication found the same in normal cells through hTERT upregulation, and separately ALT activation in breast cancer lines (Al-Dulaimi 2025). Molecular modelling and binding work from the same group proposes direct interaction of short peptides with DNA promoter regions and with LAT and PEPT family transporters for cell entry; neither is established. Effects on melatonin are not settled: perifused rat pineal glands showed no change in melatonin secretion at 10 to the minus 4 through 10 to the minus 6 M (Djeridane 2003), while the extract studies in elderly subjects report rhythm normalization. ### Evidence Preclinical: animal or in vitro data only - Induced telomerase catalytic subunit expression, telomerase activity and telomere elongation in telomerase-negative human fetal fibroblasts (Khavinson et al., 2003) - Senescing human fetal lung fibroblasts treated at passage 34 elongated their telomeres and completed about 10 further passages, past the Hayflick limit (Khavinson et al., 2004) - Independent replication in 2025: dose-dependent telomere lengthening through hTERT and telomerase upregulation in normal human cells, and ALT activation in breast cancer lines (Al-Dulaimi et al., 2025) - In female SHR mice dosed for life, mean lifespan and total tumor incidence did not change; the last decile of survivors gained 13.3%, maximum lifespan 12.3%, bone marrow chromosome aberrations fell 17.1% and leukemia incidence was 6-fold lower (Anisimov et al., 2003) - Perifused pineal glands from young and old rats showed no change in melatonin secretion at any tested concentration, with or without isoproterenol (Djeridane et al., 2003) - Human-trial status: no controlled trial of the synthetic tetrapeptide has been published and none is registered on ClinicalTrials.gov. Human exposure data are limited to in vitro work on donor lymphocytes; the 12-year randomized geroprotection study in elderly coronary patients used Epithalamin, the bovine pineal extract, not AEDG (Korkushko et al., 2006) ### References - [Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Khavinson VKh, Bondarev IE, Butyugov AA, Bulletin of Experimental Biology and Medicine, 2003](https://doi.org/10.1023/a:1025493705728) - [Peptide promotes overcoming of the division limit in human somatic cell. Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD, Bulletin of Experimental Biology and Medicine, 2004](https://doi.org/10.1023/b:bebm.0000038164.49947.8c) - [Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Al-Dulaimi S, Thomas R, Matta S, Roberts T, Biogerontology, 2025](https://doi.org/10.1007/s10522-025-10315-x) - [Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, et al., Biogerontology, 2003](https://doi.org/10.1023/a:1025114230714) - [Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Anisimov VN, Khavinson VK, Provinciali M, Alimova IN, et al., International Journal of Cancer, 2002](https://doi.org/10.1002/ijc.10570) - [Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats. Djeridane Y, Khavinson VKh, Anisimov VN, Touitou Y, Journal of Endocrinological Investigation, 2003](https://doi.org/10.1007/BF03345159) - [Overview of Epitalon: Highly Bioactive Pineal Tetrapeptide with Promising Properties. Araj SK, Brzezik J, Madra-Gackowska K, Szeleszczuk L, International Journal of Molecular Sciences, 2025](https://doi.org/10.3390/ijms26062691) - [Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyuk-Shcheglova IA, Bulletin of Experimental Biology and Medicine, 2006](https://doi.org/10.1007/s10517-006-0365-z) ### Side effects No controlled safety study of the synthetic peptide exists in any species at human-relevant doses. Lifelong dosing in mice produced no change in food consumption, body weight or total tumor incidence, and the authors described long-term administration as well tolerated in that model (Anisimov 2003). The randomized human studies reporting no adverse effects used Epithalamin, the bovine pineal extract. Commonly reported by users: injection-site irritation. One 2015 regulatory analysis identified AEDG in two illegal pharmaceutical preparations, so product identity and purity are a practical risk. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No pharmacokinetic study in any species has been published; the 2025 review of 25 years of Epitalon research reports no absorption, distribution or elimination data - Bioavailability: Not measured in any species. Rodent studies dosed intramuscularly and intranasally and reported central effects by both routes, with onset at 24 h intramuscularly and 1.5 h intranasally - Molecular weight: 390.35 Da - Sequence: AEDG ### Stacks with - [DSIP](https://peptidelabs.app/peptides/dsip/) ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Sleep](https://peptidelabs.app/peptides/category/sleep/) ## FGL-S URL: https://peptidelabs.app/peptides/fgl-s/ Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Peptide mimetic of neural cell adhesion molecule (NCAM) defined in patent filings; one published study tested it in rats and monkeys, and the memory literature belongs to its parent FGL. FGL-S is a peptide mimetic of NCAM whose structure is defined in a patent family from ENKAM rather than in a peer-reviewed paper. It appears in one published study, which measured pharmacokinetics and emotional behavior for several NCAM mimetics in rats and non-human primates. The memory, FGFR1 and neuroprotection literature in circulation is for FGL, the parent 15-residue peptide, and the human phase 1 study was of FGL-L, a different peptide. No human data exist for FGL-S. ### Benefits Cognitive support, nerve regeneration ### Dosing reference - Research dose: Vendor/community range 500 to 2000 mcg daily; no published human dose for FGL-S. - Range: 500 to 2000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Subcutaneous per vendors. The only human dosing data belong to the related FGL-L: single intranasal doses of 25, 100 and 200 mg in 24 healthy men (Anand 2007). They do not establish a dose for FGL-S. ### Mechanism Proposed by analogy: the parent FGL peptide mimics the NCAM fibronectin type III module that binds fibroblast growth factor receptor 1, and FGL-S is assumed to share that action. No mechanism study of FGL-S itself is published. The only FGL-S paper measured pharmacokinetics and emotional behavior in rats and non-human primates (Turner et al., 2019). ### Evidence Anecdotal: no peer-reviewed data - FGL-S was tested with other NCAM peptide mimetics for pharmacokinetics and emotional behavior in rats and non-human primates (Turner et al., 2019) - The structure of FGL-S is defined in ENKAM patent filings, not in a peer-reviewed paper - Rodent memory, LTP and neuroprotection findings in circulation used the parent FGL peptide, not FGL-S - Human-trial status: none for FGL-S. A different NCAM mimetic, FGL-L (FGLL), was given intranasally at 25 to 200 mg to healthy volunteers in a phase 1 tolerability and pharmacokinetic study (Anand et al., 2007) ### References - [Neural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates. Turner CA, Lyons DM, Buckmaster CL, et al., Neuropsychopharmacology, 2019](https://doi.org/10.1038/s41386-018-0052-6) - [Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers. Anand R, Seiberling M, Kamtchoua T, et al., Clinical Pharmacokinetics, 2007](https://doi.org/10.2165/00003088-200746040-00007) ### Side effects No human safety data; effects unknown beyond animal studies, where FGL peptides were tolerated in rodents at the doses tested. The exact identity of material sold under this name is unclear in the literature, which adds product risk. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No human data. Rat and primate pharmacokinetics were reported for NCAM mimetics (Turner et al., 2019); an FGL-S value was not extracted in this audit - Bioavailability: Not established in humans; no published bioavailability figure for FGL-S ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [Selank](https://peptidelabs.app/peptides/selank/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Follistatin-315 URL: https://peptidelabs.app/peptides/follistatin-315/ Also known as: FS315, Follistatin short form, Circulating follistatin Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Mature circulating form of follistatin (315 residues), a glycoprotein that binds activin strongly and myostatin weakly; muscle-mass gains come from transgenic and gene-transfer animals, not injected protein. Follistatin is an activin-binding glycoprotein. The FST gene makes two precursors by alternative splicing, 344 and 317 residues (Shimasaki 1988); after the signal peptide is removed these give the mature proteins FS315 and FS288. FS315 is the circulating form, with low affinity for cell-surface heparan sulfate, while the shorter FS288 sticks to cell surfaces (Sugino 1993). Follistatin binds activin A with high affinity and myostatin and GDF-11 considerably more weakly (Schneyer 2008). Transgenic mice over-expressing follistatin in muscle gained mass comparable to myostatin-knockout mice (Lee and McPherron 2001), and one AAV injection of follistatin raised muscle mass and strength in normal and dystrophic mice for over two years (Haidet 2008). No study has injected follistatin protein as a drug, in animals or humans. ### Benefits Muscle mass and strength in transgenic mice and after AAV gene transfer (rodent, >2 years of effect); activin and myostatin neutralisation in vitro. No study of injected follistatin protein in any species and no human data. ### Dosing reference - Research dose: No dosing data in any species; research-community range 100 to 300 mcg daily in 10 to 30 day cycles - Range: 100 to 300 mcg, 1x daily for 10-30 days - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 1 mg Short cycles. Very expensive. No human dosing data exists. Systemic activin blockade also suppresses FSH and affects reproductive signalling; research-grade material is frequently mislabeled or biologically inactive. ### Mechanism Follistatin binds TGF-beta superfamily ligands and blocks them from reaching activin type II receptors. Affinity is not uniform: it binds activin A tightly and myostatin (GDF-8) and GDF-11 much less so, which is why follistatin-based muscle effects come with activin-pathway effects such as FSH suppression (Schneyer 2008; Sugino 1993). FS315 is the mature secreted form with four EGF-like domains and little heparan-sulfate affinity, so it circulates rather than concentrating on cell surfaces (Shimasaki 1988; Sugino 1993). Blocking myostatin signaling through ActRIIB removes a brake on muscle growth: transgenic muscle-specific follistatin expression produced dramatic muscle-mass increases in mice, matching myostatin knockouts (Lee and McPherron 2001). ### Evidence Preclinical: animal or in vitro data only - Transgenic mice expressing follistatin under a skeletal-muscle promoter showed muscle-mass increases comparable to myostatin-knockout mice (Lee and McPherron, 2001) - A single AAV administration of follistatin or other myostatin inhibitors increased muscle mass and strength in normal and dystrophic mice for more than two years, including in aged animals (Haidet et al., 2008) - Follistatin binds activin A with much higher affinity than myostatin or GDF-11, so activin-pathway effects are inseparable from the muscle effect (Schneyer et al., 2008) - The FST gene yields 344- and 317-residue precursors by alternative splicing, giving the mature FS315 and FS288 proteins (Shimasaki et al., 1988) - FS288, the carboxy-terminal truncated form, binds granulosa-cell heparan sulfate proteoglycans far more tightly than FS315, which is why FS315 is the circulating species (Sugino et al., 1993) - Human-trial status: none for injected follistatin protein. The only human data are AAV1-FS344 gene-therapy trials (see Follistatin-344) ### References - [Primary structure of the human follistatin precursor and its genomic organization. Shimasaki S, Koga M, Esch F, et al., Proceedings of the National Academy of Sciences, 1988](https://doi.org/10.1073/pnas.85.12.4218) - [Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell. Sugino K, Kurosawa N, Nakamura T, et al., Journal of Biological Chemistry, 1993](https://doi.org/10.1016/s0021-9258(18)82296-7) - [Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. Schneyer AL, Sidis Y, Gulati A, et al., Endocrinology, 2008](https://doi.org/10.1210/en.2008-0259) - [Regulation of myostatin activity and muscle growth. Lee SJ, McPherron AC, Proceedings of the National Academy of Sciences, 2001](https://doi.org/10.1073/pnas.151270098) - [Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Haidet AM, Rizo L, Handy C, et al., Proceedings of the National Academy of Sciences, 2008](https://doi.org/10.1073/pnas.0709144105) - [Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Campbell C, McMillan HJ, Mah JK, et al., Muscle & Nerve, 2017](https://doi.org/10.1002/mus.25268) ### Side effects No human or animal safety data exist for injected follistatin protein. Follistatin binds activin A much more tightly than myostatin (Schneyer 2008), and activin blockade affects FSH secretion and, in other drugs of this pathway, vascular integrity: ACE-031, a different activin-receptor blocker, was stopped in trials for nosebleeds and telangiectasia (Campbell 2017). Most research-grade material is E. coli-derived and may be inactive or endotoxin-bearing, which is the more immediate practical risk. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured for injected follistatin in any species - Molecular weight: 34754.3 Da ### Stacks with - [IGF-1 LR3](https://peptidelabs.app/peptides/igf-1-lr3/) - [MGF (IGF-1 Ec)](https://peptidelabs.app/peptides/mgf-igf-1-ec/) ### Categories - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## Follistatin-344 URL: https://peptidelabs.app/peptides/follistatin-344/ Also known as: FS344, Full-length follistatin Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview The 344-residue follistatin precursor, which yields mature circulating follistatin (FS315) after its signal peptide is cut; the human evidence is AAV1-FS344 gene therapy delivering the gene, not an injected protein. FS344 is one of two follistatin precursors produced by alternative splicing of the FST gene (344 and 317 residues); removing the 29-residue signal peptide gives mature FS315 and FS288 (Shimasaki 1988). The FS344 transcript is what gene-therapy programmes deliver: AAV1.CMV.FS344 was injected into the quadriceps of six Becker muscular dystrophy patients at 3 or 6 x 10^11 vg/kg per leg, where four of six improved 6-minute walk distance by 29 to 125 m with no adverse events (Mendell 2015; Al-Zaidy 2015), and the same vector in six sporadic inclusion body myositis patients gave a reported +56.0 m/year against -25.8 m/year in matched untreated subjects (Mendell 2017). That result was publicly disputed on grounds of control selection and open-label design (Greenberg 2017). Nothing has been injected as follistatin protein in a human study. ### Benefits Improved 6-minute walk distance after AAV1-FS344 gene therapy in small open-label trials (Becker muscular dystrophy n=6, sporadic inclusion body myositis n=6, both contested); muscle mass and strength after AAV follistatin in mice. No injected-protein data. ### Dosing reference - Research dose: No dosing data for follistatin protein in any species; research-community range 100 to 300 mcg daily in 10 to 30 day cycles. The human trials dosed an AAV vector (3 to 6 x 10^11 vg/kg per leg), not a peptide - Range: 100 to 300 mcg, 1x daily for 10-30 days - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 1 mg No human dosing data for injected follistatin protein; community protocols use short cycles. FS344 is the precursor of circulating FS315, not a tissue-retained variant. Follistatin binds activin A more tightly than myostatin, so activin-pathway effects including FSH suppression come with it (Schneyer 2008). Research-grade material is frequently mislabeled or biologically inactive. ### Mechanism FS344 is a precursor: its 29-residue signal peptide is removed to give mature 315-residue follistatin, the circulating form with low heparan-sulfate affinity (Shimasaki 1988). The shorter FS288, not FS344, is the heparin-binding form that concentrates on cell surfaces, so the idea that FS344 provides tissue-specific retention is backwards. Mature follistatin binds activin A tightly and myostatin and GDF-11 more weakly, blocking them from activin type II receptors (Schneyer 2008). Gene-therapy programmes chose the FS344 splice form specifically to reduce off-target cell-surface binding (Mendell 2015). Removing the myostatin brake on muscle growth is what produced large muscle gains in follistatin-transgenic mice (Lee and McPherron 2001). ### Evidence Preclinical: animal or in vitro data only - AAV1.CMV.FS344 injected into both quadriceps of six Becker muscular dystrophy patients (3 or 6 x 10^11 vg/kg per leg): four improved 6-minute walk distance by 29 to 125 m, two did not, with reduced endomysial fibrosis on biopsy and no adverse events (Mendell et al., 2015) - Follow-up of the same cohort reported sustained ambulation gains (Al-Zaidy et al., 2015) - The same vector in six sporadic inclusion body myositis patients gave a reported +56.0 m/year on the 6-minute walk against -25.8 m/year in eight matched untreated subjects (Mendell et al., 2017) - That inclusion-body-myositis result was publicly contested over control selection and the open-label design (Greenberg, 2017) - One AAV administration of follistatin increased muscle mass and strength in normal and dystrophic mice for over two years (Haidet et al., 2008) - Human-trial status: two small open-label AAV1-FS344 gene-therapy trials, one disputed. No trial of injected follistatin protein, and no regulatory approval ### References - [A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mendell JR, Sahenk Z, Malik V, et al., Molecular Therapy, 2015](https://doi.org/10.1038/mt.2014.200) - [Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy. Al-Zaidy SA, Sahenk Z, Rodino-Klapac LR, et al., Journal of Neuromuscular Diseases, 2015](https://doi.org/10.3233/JND-150083) - [Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes. Mendell JR, Sahenk Z, Al-Zaidy S, et al., Molecular Therapy, 2017](https://doi.org/10.1016/j.ymthe.2017.02.015) - [Unfounded Claims of Improved Functional Outcomes Attributed to Follistatin Gene Therapy in Inclusion Body Myositis. Greenberg SA, Molecular Therapy, 2017](https://doi.org/10.1016/j.ymthe.2017.09.002) - [Primary structure of the human follistatin precursor and its genomic organization. Shimasaki S, Koga M, Esch F, et al., Proceedings of the National Academy of Sciences, 1988](https://doi.org/10.1073/pnas.85.12.4218) - [Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Haidet AM, Rizo L, Handy C, et al., Proceedings of the National Academy of Sciences, 2008](https://doi.org/10.1073/pnas.0709144105) - [Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. Schneyer AL, Sidis Y, Gulati A, et al., Endocrinology, 2008](https://doi.org/10.1210/en.2008-0259) - [Regulation of myostatin activity and muscle growth. Lee SJ, McPherron AC, Proceedings of the National Academy of Sciences of the United States of America, 2001](https://doi.org/10.1073/pnas.151270098) ### Side effects No safety data exist for injected follistatin protein. In the AAV1-FS344 gene-therapy trials no adverse effects were reported in six Becker muscular dystrophy patients (Mendell 2015). Follistatin binds activin A much more tightly than myostatin (Schneyer 2008), and blocking this pathway with ACE-031 caused nosebleeds and telangiectasia severe enough to stop a trial in boys with Duchenne muscular dystrophy. Research-grade material is frequently inactive or mislabeled, adding contamination risk. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured for injected follistatin protein; the AAV gene-therapy construct produces protein for months to years (mouse, >2 years) - Molecular weight: 38007.2 Da ### Stacks with - [IGF-1 LR3](https://peptidelabs.app/peptides/igf-1-lr3/) - [MGF (IGF-1 Ec)](https://peptidelabs.app/peptides/mgf-igf-1-ec/) ### Categories - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## FOXO4-DRI URL: https://peptidelabs.app/peptides/foxo4-dri/ Also known as: FOXO4-p53 interfering peptide, Senolytic peptide Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Cell-penetrating D-retro-inverso peptide that blocks the FOXO4-p53 interaction, shown in aged mice to selectively kill senescent cells and restore renal function and fitness. FOXO4-DRI is a 46-residue all-D retro-inverso peptide, built from a FOXO4 segment plus a cationic cell-penetrating carrier, designed to block the FOXO4 interaction with p53 (Baar 2017). In that paper it killed senescent but not control IMR90 human fibroblasts, and in mice given 5 mg/kg intravenously or intraperitoneally on 3 alternate days it neutralized doxorubicin liver toxicity and restored fitness, fur density and renal markers in fast-aging XpdTTD/TTD and naturally aged animals. Later work extended it to aged mouse Leydig cells, spermatogenesis and keloid fibroblasts. One result cuts the other way: in mice and rats, clearing senescent pulmonary endothelial cells with FOXO4-DRI or ABT263 worsened pulmonary hemodynamics (Born 2023). No human study exists and none is registered. ### Benefits Selective apoptosis of senescent cells (human cells in vitro), restored fitness, fur density and renal function in fast-aging and naturally aged mice, improved testosterone output and spermatogenesis in aged mice. No human data by any route ### Dosing reference - Research dose: 5 to 10 mg: vendor and community range, no published human dose. Mouse studies used 5 mg/kg intravenously or intraperitoneally on alternate days - Range: 5000 to 10000 mcg, 1x daily (short cycles) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg No human data by any route. The published mouse regimen was 3 doses of 5 mg/kg, intravenous or intraperitoneal, on days 1, 3 and 5, from a 5 mg/mL solution in PBS (Baar 2017), not daily subcutaneous dosing. The 5 to 10 mg figure sold to researchers is a scaled guess with no safety validation. Senolysis is not uniformly beneficial: clearing senescent pulmonary endothelial cells with this peptide worsened pulmonary hemodynamics in mice and rats (Born 2023). ### Mechanism Senescent cells keep p53 in the nucleus through an interaction with FOXO4, which blocks apoptosis. FOXO4-DRI competes for that interaction, p53 is excluded from the nucleus and cell-intrinsic apoptosis follows, selectively in senescent cells (Baar 2017). Solution NMR has since mapped the binding: FOXO4-DRI, itself disordered, binds the disordered second transactivation domain of p53 and forms a transiently folded complex, with the cationic cell-penetrating segment contributing to the interaction rather than only carrying the peptide across the membrane, and p53 phosphorylation increasing affinity for both FOXO4 and the peptide (Bourgeois 2025). The retro-inverso all-D design was chosen for protease resistance; no measurement of its stability or exposure in an animal has been published. ### Evidence Preclinical: animal or in vitro data only - Killed senescent human IMR90 fibroblasts while sparing control cells, with potency increasing over consecutive rounds of treatment; in mice, 3 doses of 5 mg/kg on alternate days neutralized doxorubicin liver toxicity and restored fitness, fur density and renal markers in fast-aging and naturally aged animals (Baar et al., 2017) - In naturally aged mice, FOXO4-DRI induced apoptosis in senescent Leydig cells, reduced senescence-associated secretion and raised testosterone output (Zhang et al., 2020) - In aged mice it improved sperm quality and spermatogenesis, with reduced senescence-associated secretion from Leydig cells (Li et al., 2024) - In human chondrocytes expanded to population doubling level 9 it removed over half the cells and lowered the senescence level, but did not improve chondrogenic potential (Huang et al., 2021) - Contrary result: in SM22-5-HTT+ mice and monocrotaline rats, senolytic clearance of pulmonary endothelial cells with FOXO4-DRI or ABT263 raised right ventricular systolic pressure and worsened vessel remodeling (Born et al., 2023) - Human-trial status: no human study of FOXO4-DRI has been published and no trial is registered on ClinicalTrials.gov. The mechanism has an active commercial program (Cleara Biotech) and patents, but no clinical candidate has entered trials ### References - [Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Baar MP, Brandt RMC, Putavet DA, Klein JDD, et al., Cell, 2017](https://doi.org/10.1016/j.cell.2017.02.031) - [The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Bourgeois B, Spreitzer E, Platero-Rochart D, Paar M, et al., Nature Communications, 2025](https://doi.org/10.1038/s41467-025-60844-9) - [FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Zhang C, Xie Y, Chen H, Lv L, et al., Aging (Albany NY), 2020](https://doi.org/10.18632/aging.102682) - [FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells. Li Y, Zhang C, Cheng H, Lv L, et al., Experimental Gerontology, 2024](https://doi.org/10.1016/j.exger.2024.112522) - [Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Huang Y, He Y, Makarcyzk MJ, Lin H, Frontiers in Bioengineering and Biotechnology, 2021](https://doi.org/10.3389/fbioe.2021.677576) - [FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Kong YX, Li ZS, Liu YB, Pan B, et al., Communications Biology, 2025](https://doi.org/10.1038/s42003-025-07738-0) - [Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression. Born E, Lipskaia L, Breau M, Houssaini A, et al., Circulation, 2023](https://doi.org/10.1161/CIRCULATIONAHA.122.058794) - [FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Liu Y, Hou Q, Wang R, Liu Y, et al., Naunyn-Schmiedeberg's Archives of Pharmacology, 2023](https://doi.org/10.1007/s00210-023-02452-2) ### Side effects No human safety data exist. In mice the published doses were described as well tolerated, with no weight loss over the dosing window (Baar 2017). The principal published risk is not off-target apoptosis but the senolysis itself: eliminating senescent pulmonary endothelial cells worsened pulmonary hemodynamics and vessel remodeling in two rodent models (Born 2023). FDA lists several research peptides sold through the same channels on its compounding safety-risk page; FOXO4-DRI itself is not named there. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in any species. The all-D retro-inverso backbone was chosen to resist proteolysis, and the paper reports no pharmacokinetic data; dosing on alternate days was an empirical schedule - Bioavailability: Not measured. Published animal dosing was intravenous or intraperitoneal; no subcutaneous or oral study exists. Cell entry in vitro is carried by the cationic C-terminal segment, which also contributes to p53 binding - Molecular weight: 5358.2 Da - Sequence: ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg (46 residues, all D-configuration, retro-inverso; lower case denotes D-amino acids. The C-terminal krppprrrqrrkkrg segment is the cell-penetrating carrier) ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## Fragment 176-191 + Mod GRF + Ipamorelin URL: https://peptidelabs.app/peptides/fragment-176-191-mod-grf-ipamorelin/ Also known as: Fat Loss Stack, Recomp Blend, Frag/Mod/Ipa, Fragment 176-191 + CJC-1295 + Ipamorelin Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of a GH fragment sold as 176-191, Mod GRF 1-29 and ipamorelin (12 mg: 6/3/3 mg); fat-loss claims rest on rodent data, and no study has tested the mix. Sold as a 12 mg vial: 6 mg GH fragment, 3 mg Mod GRF 1-29 (CJC-1295 without DAC) and 3 mg ipamorelin. True hGH 176-191 starts with Phe; vendor 'Fragment 176-191' often lists the AOD9604 sequence, which starts with Tyr, so the exact fragment in a vial is uncertain. The one study of hGH 176-191 itself found a brief rise in blood glucose in rats (Ng 1978); related fragments cut fat gain in obese rodents, and six human AOD9604 trials published safety but no efficacy. Mod GRF 1-29 has no study of its own, and ipamorelin has one human PK study and a negative phase 2 ileus trial (Beck 2014). No study has tested any two of these together. FDA lists ipamorelin in category 2 for 503B outsourcing, and CJC-1295 and AOD-9604 in the withdrawn-nomination table of its compounding safety-risk page. ### Benefits Reduced fat gain (rodent, related hGH fragments); GH release (human, ipamorelin IV; inferred for Mod GRF 1-29); human trials of the analog AOD9604 published only safety. No data for the blend ### Dosing reference - Research dose: 350 to 700 mcg of blend per injection (about 175 to 350 mcg fragment and 90 to 175 mcg each of Mod GRF 1-29 and ipamorelin at the 6/3/3 mg ratio), 1 to 2x daily: vendor/community range, no published human dose of the blend, hGH 176-191 or Mod GRF 1-29 - Range: 350 to 700 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 12 mg Subcutaneous in community use, often fasted in the morning or at bedtime. The earlier statement that AOD9604 failed against placebo in 12-week trials is not supported by published data: only safety results of the AOD9604 obesity trials were published (Stier 2013). Human ipamorelin doses were IV (0.03 mg/kg twice daily in the ileus trial); no human dose of hGH 176-191 or Mod GRF 1-29 exists. ### Mechanism Proposed, from component studies. The hGH fragment is the C-terminal end of growth hormone; related fragments raised fat oxidation in obese mice without binding the hGH receptor (Heffernan 2001), while hGH 176-191 itself raised blood glucose and insulin briefly in rats (Ng 1978). Mod GRF 1-29 is a tetrasubstituted GHRH(1-29) analog acting on the pituitary GHRH receptor; its activity has not been measured directly. Ipamorelin is a ghrelin-receptor agonist that released GH without raising ACTH or cortisol in swine (Raun 1998). The idea that the fragment adds direct lipolysis to a GH pulse from the other two has not been tested. ### Evidence Preclinical: animal or in vitro data only - hGH 176-191 caused a short-lived rise in blood glucose and a more sustained rise in insulin in rats (Ng and Bornstein, 1978) - Chronic treatment with the tyrosine analog AOD9604 raised fat oxidation and reduced weight in obese mice without hyperglycaemia (Heffernan et al., 2001) - Six placebo-controlled human AOD9604 trials (about 900 adults, oral or IV) found no change in IGF-1 or glucose tolerance; only safety results were published (Stier et al., 2013) - IV ipamorelin in 40 healthy men gave a single GH peak at 40 min with a 2 h terminal half-life (Gobburu et al., 1999) - D-Ala2 substitution in Mod GRF 1-29 raised the plasma half-time of GHRH(1-29) only from 4.3 to 6.7 min in men (Soule et al., 1994) - Human-trial status: no study has tested the blend as sold or any pair within it. Ipamorelin's only RCT, in postoperative ileus, was negative (Beck et al., 2014); AOD9604 human data are for that analog, not hGH 176-191 ### References - [Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Ng FM, Bornstein J, American Journal of Physiology, 1978](https://doi.org/10.1152/ajpendo.1978.234.5.E521) - [Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan MA, Thorburn AW, Fam B, et al., International Journal of Obesity and Related Metabolic Disorders, 2001](https://doi.org/10.1038/sj.ijo.0801740) - [Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Stier H, Vos E, Kenley D, Journal of Endocrinology and Metabolism, 2013](https://doi.org/10.4021/jem157w) - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Jette L, Leger R, Thibaudeau K, et al., Endocrinology, 2005](https://doi.org/10.1210/en.2004-1286) - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) - [Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999](https://doi.org/10.1023/a:1018955126402) - [Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014](https://doi.org/10.1007/s00384-014-2030-8) ### Side effects No human safety study of the blend, of hGH 176-191 or of Mod GRF 1-29 has been published. In rats hGH 176-191 briefly raised blood glucose and insulin (Ng 1978). In AOD9604 trials headache and GI effects occurred at placebo-like rates (Stier 2013), and IV ipamorelin was well tolerated in a phase 2 trial (Beck 2014). Commonly reported by users (anecdotal): injection-site irritation, water retention, joint aches, head rush. Ipamorelin is in category 2 of FDA's 503B interim policy (added 2023-09-29), and ipamorelin, CJC-1295 and AOD-9604 are in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. FDA cites serious adverse events with CJC-1295, including increased heart rate and a systemic vasodilatory reaction. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: hGH fragment: not published. Mod GRF 1-29 not measured; D-Ala2-GHRH(1-29) ~6.7 min (human, IV). Ipamorelin ~2 h terminal (human, IV) - Bioavailability: Not measured by subcutaneous injection for any component; human ipamorelin data are IV and AOD9604 trials used oral or IV dosing ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## GH Fragment 176-191 URL: https://peptidelabs.app/peptides/gh-fragment-176-191/ Also known as: HGH Frag 176-191, HGH Fragment 176-191, hGH(176-191) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic C-terminal fragment of human growth hormone (residues 176-191). Related fragments cut fat gain in obese rodents; the one study of 176-191 itself found a brief rise in blood glucose in rats. GH Fragment 176-191 is the last 16 residues of human growth hormone, FLRIVQCRSVEGSCGF. Monash University work from the 1970s on found that C-terminal hGH fragments affect fat and glucose metabolism. In rats, hGH 176-191 and related fragments caused a short-lived rise in blood glucose and insulin, and fragments containing 178-191 reduced insulin sensitivity (Ng 1978). The shorter hGH 177-191 had antilipogenic activity in rat fat (Wu 1993) and reduced weight gain and fat mass in obese mice (Natera 1994). The tyrosine analog AOD9604 was the version taken forward; it did not alter glucose in rodents or humans (Heffernan 2001). No human study of hGH 176-191 itself exists. Products sold under this name often list the AOD9604 sequence. ### Benefits Antilipogenic activity (rat fat tissue, hGH 177-191), reduced weight gain and fat mass (obese mice, hGH 177-191), raised fat oxidation (obese mice, AOD9604 analog); no human data for this fragment ### Dosing reference - Research dose: 250 to 500 mcg 2 to 3 times daily (vendor/community range, no published human dose) - Range: 250 to 500 mcg, 2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Community protocols inject subcutaneously, often fasted. No human dose of hGH 176-191 has been published; rodent work dosed by weight (5 nmol/kg IV in rats, Ng 1978). Human trials used the AOD9604 analog, orally or IV (Stier 2013). ### Mechanism The C-terminal region of hGH carries its lipolytic and antilipogenic activity. hGH 177-191 inhibited lipogenesis in rat adipose tissue without measurable lipolysis (Wu 1993); a 177-191 analog stimulated hormone-sensitive lipase and inhibited acetyl-CoA carboxylase in rat fat (Ng 2000, J Mol Endocrinol). The related AOD9604 does not bind the GH receptor (Heffernan 2001). For hGH 176-191 specifically, the only data show acute hyperglycaemic and insulin-raising effects in rats (Ng 1978), so a glucose-neutral profile is not established for this fragment. Beta-3-adrenergic involvement is not supported; AOD9604 acted independently of that receptor (Heffernan 2001). ### Evidence Preclinical: animal or in vitro data only - hGH 176-191 and related C-terminal fragments caused a short-lived rise in blood glucose and a more sustained rise in insulin in rats; fragments with residues 178-191 reduced insulin sensitivity (Ng and Bornstein, 1978) - hGH 177-191 matched the antilipogenic activity of intact hGH in rat fat pads (Wu and Ng, 1993) - Chronic hGH 177-191 reduced weight gain and fat mass in obese ob/ob mice (Natera et al., 1994) - Contested: the tyrosine analog AOD9604 did not raise glucose in obese mice (Heffernan et al., 2001) or in human trials (Stier et al., 2013), unlike the 1978 result for 176-191 - Human-trial status: none for hGH 176-191; human trials were run only with AOD9604 ### References - [Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Ng FM, Bornstein J, American Journal of Physiology, 1978](https://doi.org/10.1152/ajpendo.1978.234.5.E521) - [Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Wu Z, Ng FM, Biochemistry and Molecular Biology International, 1993](https://pubmed.ncbi.nlm.nih.gov/8358331/) - [Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Natera SH, Jiang WJ, Ng FM, Biochemistry and Molecular Biology International, 1994](https://pubmed.ncbi.nlm.nih.gov/7987248/) - [Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. Heffernan MA, Jiang WJ, Thorburn AW, Ng FM, American Journal of Physiology - Endocrinology and Metabolism, 2000](https://doi.org/10.1152/ajpendo.2000.279.3.E501) - [Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. Ng FM, Jiang WJ, Gianello R, et al., Journal of Molecular Endocrinology, 2000](https://doi.org/10.1677/jme.0.0250287) - [Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan MA, Thorburn AW, Fam B, et al., International Journal of Obesity and Related Metabolic Disorders, 2001](https://doi.org/10.1038/sj.ijo.0801740) - [Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Stier H, Vos E, Kenley D, Journal of Endocrinology and Metabolism, 2013](https://doi.org/10.4021/jem157w) ### Side effects No human safety data for hGH 176-191. In rats it produced a short-lived rise in blood glucose and insulin (Ng 1978). The related AOD9604 showed headache and GI effects at placebo-like rates in human trials (Stier 2013). Injection-site irritation and headache are commonly reported (anecdotal). ### Storage - Storage: Refrigerate 2-8°C (36-46°F); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not published in any species - Bioavailability: Not reported. A related oral fragment (AOD9401) was active in obese mice (Heffernan 2000); no subcutaneous data - Molecular weight: 1799.1 Da - Sequence: FLRIVQCRSVEGSCGF [disulfide Cys7-Cys14] ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## GHK Basic URL: https://peptidelabs.app/peptides/ghk-basic/ Also known as: Copper-free GHK, GHK tripeptide, Apo-GHK Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Copper-free form of the human tripeptide GHK (Gly-His-Lys), studied for collagen synthesis and wound repair, though nearly all published data use the copper complex. GHK is a tripeptide first isolated from human plasma as a growth-modulating factor and synthesized in 1973 (Pickart 1973; Schlesinger 1977). The sequence occurs in the alpha-2 chain of type I collagen, which is where the wound-healing hypothesis comes from (Maquart 1988). GHK Basic is the apo form, sold without the copper ion. Nearly every published result uses the copper complex: GHK-Cu stimulated fibroblast collagen synthesis from 10 to the minus 12 M (Maquart 1988), and the proposed physiological role of the free peptide is to carry copper into cells (Pickart 1980). One 2024 commentary reports GHK alone reversing senescence markers and inducing apoptosis in myofibroblasts. The catalog also lists GHK-Cu (id 44), the copper complex, which is the molecule most of these references describe. ### Benefits Collagen synthesis in fibroblast culture, from 10 to the minus 12 M, peaking at 10 to the minus 9 M (in vitro, copper complex), wound repair in rodent and in vitro models, reversal of myofibroblast senescence markers (mouse and human cells). Copper-free GHK has no study of its own in any species ### Dosing reference - Research dose: 1 to 5 mg daily: vendor and community range, no published human dose for GHK by any route - Range: 1000 to 5000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 50 mg Copper-free apo form, sold for subcutaneous or topical research use. Published work is in cell culture at molar concentrations (collagen stimulation from 10 to the minus 12 to 10 to the minus 9 M) or in topical formulations, not at a systemic dose. No study has dosed GHK in a human by injection. Copper availability matters for activity, so results obtained with the complex do not transfer to the apo form without that caveat. ### Mechanism The proposed mechanism for the free peptide is copper transport: GHK binds copper(II) with high affinity and the 1980 Nature paper concluded that its growth-modulating activity works by facilitating copper uptake into cells (Pickart 1980), with the solution structure of the complex solved two years later (Freedman 1982). Downstream effects are reported for the complex, not the apo form: GHK-Cu raised collagen synthesis in human fibroblast cultures in a concentration range starting at 10 to the minus 12 M and independent of cell number (Maquart 1988), and the gene-expression work describing broad resets of matrix and antioxidant programs used GHK-Cu or GHK in serum-containing media where copper is available (Pickart 2015). Copper-independent activity of the apo peptide has not been demonstrated. ### Evidence Preclinical: animal or in vitro data only - GHK was isolated from human plasma as a growth-modulating factor, identified as glycyl-histidyl-lysine and reproduced synthetically (Pickart et al., 1973; Schlesinger et al., 1977) - The free tripeptide's activity was attributed to facilitating copper uptake into cells, with the structure of the copper complex solved in 1982 (Pickart et al., 1980; Freedman et al., 1982) - GHK-Cu stimulated collagen synthesis in human fibroblast cultures from 10 to the minus 12 M, maximal at 10 to the minus 9 M, with no change in cell number (Maquart et al., 1988) - GHK reversed senescence markers and induced apoptosis in myofibroblasts and improved fibroblast migration and collagen contraction in aged mouse and human cells, reported in a 2024 commentary rather than a primary trial (He et al., 2024) - Peptide-copper complexes stimulated hair follicles in C3H mice; the hair-growth literature is on complexes, not the apo peptide (Trachy et al., 1991) - Human-trial status: no clinical trial of copper-free GHK exists in any indication. The human evidence for this sequence is cosmetic and formulation work on GHK-Cu, and FDA lists GHK-Cu for injectable routes in the withdrawn-nomination table of its compounding safety-risk page as of 2026-04-22 ### References - [A synthetic tripeptide which increases survival of normal liver cells, and stimulates growth in hepatoma cells. Pickart L, Thayer L, Thaler MM, Biochemical and Biophysical Research Communications, 1973](https://doi.org/10.1016/0006-291x(73)91459-9) - [Growth-modulating serum tripeptide is glycyl-histidyl-lysine. Schlesinger DH, Pickart L, Thaler MM, Experientia, 1977](https://doi.org/10.1007/BF02002806) - [Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Pickart L, Freedman JH, Loker WJ, Peisach J, Nature, 1980](https://doi.org/10.1038/288715a0) - [Structure of the glycyl-L-histidyl-L-lysine-copper(II) complex in solution. Freedman JH, Pickart L, Weinstein B, Mims WB, Biochemistry, 1982](https://doi.org/10.1021/bi00262a004) - [Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Maquart FX, Pickart L, Laurent M, Gillery P, et al., FEBS Letters, 1988](https://doi.org/10.1016/0014-5793(88)80509-x) - [GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Pickart L, Vasquez-Soltero JM, Margolina A, BioMed Research International, 2015](https://doi.org/10.1155/2015/648108) - [The naturally occurring peptide GHK reverses age-related fibrosis by modulating myofibroblast function. He Q, Mazzola J, Ladiges W, Aging Pathobiology and Therapeutics, 2024](https://doi.org/10.31491/apt.2024.12.158) - [The hair follicle-stimulating properties of peptide copper complexes. Results in C3H mice. Trachy RE, Fors TD, Pickart L, Uno H, Annals of the New York Academy of Sciences, 1991](https://doi.org/10.1111/j.1749-6632.1991.tb24420.x) ### Side effects No systemic safety data exist for GHK by any route, and no human trial has recorded adverse events for the copper-free form. Topical cosmetic use of this sequence is reported as well tolerated in formulation studies, with irritation, redness and stinging the commonly reported complaints (anecdotal). For the copper complex by injection, FDA states it may pose a risk of immunogenicity for certain routes and that no human safety data were identified; GHK-Cu sits in the withdrawn-nomination table of that page as of 2026-04-22. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No pharmacokinetic study of GHK or GHK-Cu has been published in any species. GHK is present in human plasma and its concentration is reported to decline with age (Pickart 2015) - Bioavailability: Not measured by any route in any species. Topical delivery of this sequence is studied as a formulation problem, and the apo peptide's activity depends on binding copper once in contact with tissue - Molecular weight: 340.38 Da - Sequence: GHK (apo form, no copper ion) ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [TB-500](https://peptidelabs.app/peptides/tb-500/) ### Categories - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## GHK-Cu URL: https://peptidelabs.app/peptides/ghk-cu/ Also known as: Copper Peptide, GHK-Copper, Glycyl-L-histidyl-L-lysine:copper(II), Prezatide copper, Copper tripeptide-1 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Copper complex of the tripeptide Gly-His-Lys, isolated from human plasma in 1973; raises collagen synthesis in cell and rat studies, with mixed results in small topical human trials. GHK was isolated from human plasma in 1973 and binds copper(II) tightly. Cell and rat studies show raised collagen and glycosaminoglycan synthesis and faster wound closure. Human data are topical only: a gel helped diabetic foot ulcers close in one RCT, a 0.4% cream did no better than placebo in venous ulcers, and a 13-person post-laser study found no objective skin benefit. No injected or oral human study has been published, and a 2026 independent review calls the clinical evidence sparse. Much of the review literature comes from the discoverer's group. Same molecule as the GHK-Cu Capsule entry (id 28). Listed on FDA's 503A category 2 (safety concerns) page as GHK-Cu for injectable routes, withdrawn-nomination table, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Benefits Wound healing (topical; 1 positive RCT in diabetic foot ulcers, 1 negative in venous ulcers), collagen synthesis (cell culture, rat wounds), hair follicle growth (mouse), skin appearance (topical, no objective benefit in 1 small RCT) ### Dosing reference - Research dose: 1 to 2 mg daily SC: vendor/community range, no published human injected dose. Topical trial products included a 0.4% cream - Range: 1000 to 2000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 50 mg, 100 mg Subcutaneous injection is community practice; no injected human study has been published. Human data are topical: daily gel after debridement in diabetic foot ulcers, 0.4% cream in venous ulcers. GHK-Cu is about 16% copper by mass, so 2 mg carries about 0.3 mg copper, against a US adult upper intake level of 10 mg/day for oral copper. No parenteral limit is set for this compound. ### Mechanism Proposed. GHK binds Cu2+ with high affinity. In fibroblast culture GHK-Cu raised collagen synthesis starting at 10^-12 to 10^-11 M, maximal at 10^-9 M, independent of cell number (Maquart et al., 1988). Injected into rat wound chambers it increased collagen, glycosaminoglycans, DNA and type I and III collagen mRNA in a concentration-dependent way, without raising TGF-beta mRNA (Maquart et al., 1993). Topical gel lowered TNF-alpha, MMP-2 and MMP-9 in ischemic rat wounds (Canapp et al., 2003). Claims that GHK resets thousands of human genes come from cell-line expression database analyses in reviews by the discovering group and have not been tested in tissue. ### Evidence Preclinical: animal or in vitro data only - Collagen synthesis in fibroblast culture rose from 10^-12 M GHK-Cu and peaked at 10^-9 M, independent of cell number (Maquart et al., 1988) - In rat wound chambers GHK-Cu raised collagen, glycosaminoglycan and DNA content in a concentration-dependent way (Maquart et al., 1993) - Topical gel on ischemic rat wounds: 64.5% area reduction by day 13 vs 45.6% with vehicle and 28.2% untreated (Canapp et al., 2003) - Multicenter evaluator-blinded RCT of a GHK-Cu gel in diabetic neuropathic plantar ulcers: median closure 98.5% vs 60.8% with vehicle, infections 7% vs 34% (Mulder et al., 1994) - Evaluator-blinded RCT in venous stasis ulcers (n=86): 0.4% GHK-Cu cream was no better than placebo, while silver sulfadiazine was (Bishop et al., 1992) - Human-trial status: topical only, with mixed results; a 13-person post-laser trial found no objective benefit (Mateescu et al., 2026). No injected or oral human study. Hair claims rest on mouse data (Trachy et al., 1991). Most reviews come from the discovering group ### References - [Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Maquart FX, Pickart L, Laurent M, et al., FEBS Letters, 1988](https://doi.org/10.1016/0014-5793(88)80509-x) - [In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. Maquart FX, Bellon G, Chaqour B, et al., The Journal of Clinical Investigation, 1993](https://doi.org/10.1172/JCI116842) - [The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Canapp SO Jr, Farese JP, Schultz GS, et al., Veterinary Surgery, 2003](https://doi.org/10.1111/j.1532-950x.2003.00515.x) - [The hair follicle-stimulating properties of peptide copper complexes. Results in C3H mice. Trachy RE, Fors TD, Pickart L, et al., Annals of the New York Academy of Sciences, 1991](https://doi.org/10.1111/j.1749-6632.1991.tb24420.x) - [Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Mulder GD, Patt LM, Sanders L, et al., Wound Repair and Regeneration, 1994](https://doi.org/10.1046/j.1524-475X.1994.20406.x) - [A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. Bishop JB, Phillips LG, Mustoe TA, et al., Journal of Vascular Surgery, 1992](https://doi.org/10.1067/mva.1992.37086) - [Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Hostynek JJ, Dreher F, Maibach HI, Inflammation Research, 2011](https://doi.org/10.1007/s00011-010-0238-9) - [GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap. Mateescu DM, Gavrilescu DM, Mincioaga RI, et al., Pharmaceutics, 2026](https://doi.org/10.3390/pharmaceutics18091077) ### Side effects No controlled safety data exist for injected GHK-Cu. Topical RCTs in diabetic and venous ulcers and post-laser skin reported no specific safety signal in their abstracts, and the diabetic ulcer trial found fewer infections (7% vs 34%) (Mulder et al., 1994). FDA's category 2 entry for injectable GHK-Cu cites possible immunogenicity from aggregation and peptide-related impurities and limited human data; the nomination was later withdrawn. Copper load is a theoretical concern in disorders of copper excretion such as Wilson's disease. Commonly reported (anecdotal): injection-site stinging, redness and lumps; topical irritation. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured: no published pharmacokinetic study by any route or species - Bioavailability: Topical: in human skin in vitro, copper from GHK-Cu permeated dermatomed skin at 2.43 x 10^-4 cm/h, 136 mcg/cm2 over 48 h (Hostynek et al., 2011). Injected: not measured - Molecular weight: 402.92 Da - Sequence: GHK [Cu2+ complex] ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [TB-500](https://peptidelabs.app/peptides/tb-500/) ### Categories - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Hair Growth](https://peptidelabs.app/peptides/category/hair-growth/) - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## GHK-Cu Capsule URL: https://peptidelabs.app/peptides/ghk-cu-capsule/ Also known as: Copper tripeptide oral, GHK oral Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Oral capsule formulation of the copper tripeptide GHK-Cu; oral absorption and systemic efficacy are unestablished, with human evidence limited to topical GHK-Cu. GHK-Cu Capsule is an oral formulation of the copper-binding tripeptide GHK. The published human evidence for GHK-Cu is topical and mixed; no study in any species has shown that oral GHK-Cu survives digestion intact or reaches skin, hair follicles or connective tissue at active concentrations. Reported benefits are extrapolated from topical, rodent and cell-culture work. Same molecule as the GHK-Cu entry (id 44), which covers the injectable and topical literature. ### Benefits Reported skin, hair and anti-aging support; oral efficacy unproven ### Dosing reference - Research dose: 1 to 10 mg daily orally: vendor/community range, no published oral dose in any species - Range: 1000 to 10000 mcg, 1x daily Oral capsule. No oral study of GHK-Cu exists in any species; topical is the researched route. GHK-Cu is about 16% copper by mass, so 1 to 10 mg carries about 0.16 to 1.6 mg copper, against a US adult upper intake level of 10 mg/day for copper from food and supplements. ### Mechanism Same molecule as injectable and topical GHK-Cu. GHK binds Cu2+ with high affinity, and GHK-Cu raised collagen synthesis in fibroblast culture at 10^-12 to 10^-9 M (Maquart et al., 1988). Whether any intact GHK-Cu is absorbed after oral dosing is unknown; no oral absorption study of GHK-Cu exists in any species. ### Evidence Anecdotal: no peer-reviewed data - Collagen synthesis in fibroblast culture rose from 10^-12 M GHK-Cu and peaked at 10^-9 M (Maquart et al., 1988) - Topical GHK-Cu gel improved closure of diabetic neuropathic plantar ulcers vs vehicle (median 98.5% vs 60.8%) in a multicenter RCT (Mulder et al., 1994) - Topical 0.4% GHK-Cu cream was no better than placebo in venous stasis ulcers (n=86) (Bishop et al., 1992) - Copper from topical GHK-Cu permeated human skin in vitro at 2.43 x 10^-4 cm/h (Hostynek et al., 2011) - Human-trial status: no oral study of GHK-Cu in any species; all human data are topical, and a 2026 independent review rates the clinical evidence as sparse (Mateescu et al., 2026) ### References - [Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Maquart FX, Pickart L, Laurent M, et al., FEBS Letters, 1988](https://doi.org/10.1016/0014-5793(88)80509-x) - [Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Mulder GD, Patt LM, Sanders L, et al., Wound Repair and Regeneration, 1994](https://doi.org/10.1046/j.1524-475X.1994.20406.x) - [A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. Bishop JB, Phillips LG, Mustoe TA, et al., Journal of Vascular Surgery, 1992](https://doi.org/10.1067/mva.1992.37086) - [Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Hostynek JJ, Dreher F, Maibach HI, Inflammation Research, 2011](https://doi.org/10.1007/s00011-010-0238-9) - [GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap. Mateescu DM, Gavrilescu DM, Mincioaga RI, et al., Pharmaceutics, 2026](https://doi.org/10.3390/pharmaceutics18091077) ### Side effects No human safety data exist for oral GHK-Cu. At 1 to 10 mg the copper content (about 0.16 to 1.6 mg) is below the US adult upper intake level of 10 mg/day, which is set from liver damage seen with long-term excess intake; disorders of copper excretion such as Wilson's disease are a theoretical concern. Commonly reported (anecdotal): nausea, stomach upset. ### Storage - Storage: Room temperature - Lyophilized: 12+ months ### Pharmacology - Half-life: Not measured: no pharmacokinetic study of oral GHK-Cu in any species - Bioavailability: Oral: not measured; no oral absorption study of GHK-Cu in any species - Molecular weight: 402.92 Da - Sequence: GHK [Cu2+ complex] ### Categories - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Hair Growth](https://peptidelabs.app/peptides/category/hair-growth/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## Ghrelin URL: https://peptidelabs.app/peptides/ghrelin/ Also known as: Lenomorelin, Acyl ghrelin, Hunger hormone Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview 28-amino-acid stomach hormone and the endogenous GHS-R1a ligand; drives hunger, GH release and gastric motility in human infusion studies. Ghrelin is a 28-amino acid peptide hormone produced primarily in the stomach. It is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Research demonstrates roles in appetite regulation, GH secretion, gastric motility, and energy homeostasis. Studied for applications in cachexia, gastroparesis, and growth hormone deficiency. ### Benefits Food intake +28% (human RCT crossover, n=9), GH release (human, dose-dependent), gastric emptying in idiopathic gastroparesis (human, n=6), LV function, exercise capacity and lean mass in chronic heart failure (human, n=10, open label) ### Dosing reference - Research dose: ~1 mcg/kg IV bolus for GH release (about 70 mcg; Takaya 2000); 3.6 nmol/kg SC (about 12 mcg/kg, ~850 mcg) for appetite (Druce 2006); 2 mcg/kg IV 2x daily in heart failure (Nagaya 2004); no established research range - Range: 70 to 850 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Only Ser3-octanoylated ghrelin activates GHS-R1a; des-acyl ghrelin is inactive at this receptor (Kojima 1999). Human studies used IV bolus or infusion; one RCT showed a single SC injection of 3.6 nmol/kg raised energy intake 27% (Druce 2006). Acyl ghrelin disappears from plasma in about 10 min (Akamizu 2004). An IV dose raised glucose and lowered insulin for about 2 h in healthy men (Broglio 2001). ### Mechanism Ghrelin is a 28 amino acid orexigenic peptide primarily produced by gastric oxyntic cells. Requires octanoylation (fatty acid attachment) at Ser3 by GOAT enzyme for biological activity. Binds to GHS-R1a (growth hormone secretagogue receptor type 1a), a GPCR that couples to Gq and G12/13. In hypothalamus, stimulates appetite through NPY/AgRP neurons while inhibiting POMC neurons. In pituitary, stimulates GH release synergistically with GHRH. Also regulates gastric motility, reward pathways, and glucose homeostasis. Levels rise pre-meal and fall post-prandially. ### Evidence Clinical: at least one published human trial or an approved drug - Identified as the endogenous GHS-R ligand; a 28-residue stomach peptide whose Ser3 octanoyl group is required for activity (Kojima et al., 1999) - IV 0.2-5 mcg/kg released GH dose-dependently (peak 107 ng/mL at 5 mcg/kg) and raised ACTH, cortisol and prolactin in 4 men (Takaya et al., 2000) - IV infusion increased buffet energy intake 28% in every subject in a randomized double-blind crossover, n=9 (Wren et al., 2001) - Acyl ghrelin half-life 9-13 min, total ghrelin 27-31 min after IV bolus; adverse effects transient (Akamizu et al., 2004) - 3 weeks of 2 mcg/kg IV twice daily improved LV ejection fraction, peak VO2 and lean mass in 10 chronic heart failure patients (Nagaya et al., 2004) - Human-trial status: ghrelin itself is not approved anywhere; the ghrelin-receptor agonist anamorelin was approved in Japan (Adlumiz, 22 Jan 2021) for cancer cachexia after the ROMANA phase 3 trials, and is not FDA-approved ### References - [Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K, Nature, 1999](https://doi.org/10.1038/45230) - [Ghrelin strongly stimulates growth hormone release in humans. Takaya K, Ariyasu H, Kanamoto N, et al., Journal of Clinical Endocrinology & Metabolism, 2000](https://doi.org/10.1210/jcem.85.12.7167) - [Ghrelin enhances appetite and increases food intake in humans. Wren AM, Seal LJ, Cohen MA, et al., Journal of Clinical Endocrinology & Metabolism, 2001](https://doi.org/10.1210/jcem.86.12.8111) - [Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. Broglio F, Arvat E, Benso A, et al., Journal of Clinical Endocrinology & Metabolism, 2001](https://doi.org/10.1210/jcem.86.10.8098) - [Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects. Akamizu T, Takaya K, Irako T, et al., European Journal of Endocrinology, 2004](https://doi.org/10.1530/eje.0.1500447) - [Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Nagaya N, Moriya J, Yasumura Y, et al., Circulation, 2004](https://doi.org/10.1161/01.CIR.0000149746.62908.BB) - [Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Tack J, Depoortere I, Bisschops R, Verbeke K, Janssens J, Peeters T, Alimentary Pharmacology & Therapeutics, 2005](https://doi.org/10.1111/j.1365-2036.2005.02658.x) - [Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers. Druce MR, Neary NM, Small CJ, et al., International Journal of Obesity (London), 2006](https://doi.org/10.1038/sj.ijo.0803158) ### Side effects In a placebo-controlled study of 1-5 mcg/kg IV, adverse effects were transient and no more frequent than placebo (Akamizu 2004). Documented acute effects in humans: increased hunger and food intake (Wren 2001), a rise in blood glucose with a fall in insulin lasting about 2 h (Broglio 2001), and rises in ACTH, cortisol and prolactin (Takaya 2000). Flushing, sweating and a mild drop in blood pressure are commonly reported (anecdotal). ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: 9-13 min acyl ghrelin, 27-31 min total ghrelin (human, IV bolus; Akamizu 2004) - Bioavailability: SC injection of 3.6 nmol/kg was active on energy intake (human; Druce 2006); no absolute bioavailability figure located - Molecular weight: 3370.9 Da - Sequence: GS[S(n-octanoyl)]FLSPEHQRVQQRKESKKPPAKLQPR ### Stacks with - [GHRP-6](https://peptidelabs.app/peptides/ghrp-6/) - [MK-677](https://peptidelabs.app/peptides/mk-677/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## GHRH URL: https://peptidelabs.app/peptides/ghrh/ Also known as: GRF, Somatoliberin, GHRH(1-44) Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Native hypothalamic hormone (somatorelin, GHRH 1-44) that triggers GH release from pituitary somatotrophs; used clinically as a diagnostic GH-stimulation agent. Growth hormone-releasing hormone (somatorelin, GRF) is the 44-residue hypothalamic peptide that drives pituitary GH secretion. It was isolated in 1982 from pancreatic tumors causing acromegaly (Guillemin 1982; Rivier 1982). Plasma dipeptidyl peptidase cleaves the N-terminal Tyr-Ala within minutes, leaving an inactive GHRH(3-44) (Frohman 1986). Its main clinical role is diagnostic: GHRH 1 mcg/kg IV plus arginine is a validated test for adult GH deficiency, with BMI-specific cut-offs (Aimaretti 1998; Corneli 2005). Nocturnal pulsatile SC GHRH(1-40) accelerated growth in 3 of 5 GH-deficient children (Smith 1986). The approved drugs built on it are the 1-29 fragment sermorelin and the stabilized 1-44 analog tesamorelin. ### Benefits GH release and pituitary reserve testing (human, GHRH-arginine test validated in hundreds of patients), growth acceleration in GH-deficient children with pulsatile dosing (human, n=5, open label), reference ligand for GH-axis research ### Dosing reference - Research dose: 1 mcg/kg IV (diagnostic GHRH-arginine test, about 70-100 mcg); 1-2 mcg/kg per SC pulse in a pediatric treatment study; research-community range 100-200 mcg SC nightly - Range: 100 to 200 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Native GHRH(1-44). IV bolus in diagnostic testing; SC in the pediatric pulsatile study. Intact peptide disappears from plasma with a half-life of about 7 min, so each injection gives one brief GH pulse (Frohman 1986). Facial flushing lasting 1-3 min occurred in 16 of 18 men given 1 mcg/kg IV (Bowers 1990). ### Mechanism GHRH (Growth Hormone Releasing Hormone, also called GRF or somatoliberin) is a 44 amino acid peptide from the hypothalamus that stimulates GH secretion from pituitary somatotrophs. Binds to GHRH-R, a G-protein coupled receptor, activating adenylyl cyclase and cAMP production. This triggers calcium influx and GH granule exocytosis. Native GHRH has a very short half-life (~7-10 minutes) due to DPP-IV cleavage, necessitating development of more stable analogs like CJC-1295 and tesamorelin. ### Evidence Clinical: at least one published human trial or an approved drug - Isolated and sequenced from pancreatic tumors causing acromegaly (Guillemin et al., 1982; Rivier et al., 1982) - Plasma clearance 194 L/m2/day; elimination-phase half-life of immunoreactive GRF 52 min after IV injection in men (Frohman et al., 1984) - Intact GHRH(1-44) half-life 6.8 min in vivo; cleaved to inactive GHRH(3-44) by a plasma dipeptidylaminopeptidase (Frohman et al., 1986) - Nocturnal pulsatile SC GHRH(1-40) raised growth velocity from 3.7 to 7.2 cm/year in 3 of 5 GH-deficient children (Smith et al., 1986) - GHRH + arginine test is as sensitive as insulin hypoglycemia for adult GH deficiency, with BMI-specific cut-offs from 640 subjects (Aimaretti et al., 1998; Corneli et al., 2005) - Human-trial status: used clinically as a diagnostic stimulus; the approved therapeutics are its analogs sermorelin (1997) and tesamorelin (2010) ### References - [Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Guillemin R, Brazeau P, Bohlen P, Esch F, Ling N, Wehrenberg WB, Science, 1982](https://doi.org/10.1126/science.6812220) - [Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Rivier J, Spiess J, Thorner M, Vale W, Nature, 1982](https://doi.org/10.1038/300276a0) - [Metabolic clearance and plasma disappearance rates of human pancreatic tumor growth hormone releasing factor in man. Frohman LA, Thominet JL, Webb CB, et al., Journal of Clinical Investigation, 1984](https://doi.org/10.1172/JCI111333) - [Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM, Journal of Clinical Investigation, 1986](https://doi.org/10.1172/JCI112679) - [Nocturnal pulsatile growth hormone releasing hormone treatment in growth hormone deficiency. Smith PJ, Brook CG, Rivier J, Vale W, Thorner MO, Clinical Endocrinology (Oxford), 1986](https://doi.org/10.1111/j.1365-2265.1986.tb03593.x) - [Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. Aimaretti G, Corneli G, Razzore P, et al., Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.5.4837) - [The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Corneli G, Di Somma C, Baldelli R, et al., European Journal of Endocrinology, 2005](https://doi.org/10.1530/eje.1.01967) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) ### Side effects Transient facial flushing (1-3 min) in 16 of 18 men after 1 mcg/kg IV (Bowers 1990). No adverse effects reported in the pediatric pulsatile study (Smith 1986). Injection-site redness, headache, water retention, joint aches and reduced insulin sensitivity are commonly reported (anecdotal) with sustained GH elevation. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~7 min for intact GHRH(1-44) (human, IV; HPLC, Frohman 1986); immunoreactive elimination phase ~52 min (human, IV; Frohman 1984) - Molecular weight: 5040.4 Da - Sequence: YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL[NH2] ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) ## GHRP-2 URL: https://peptidelabs.app/peptides/ghrp-2/ Also known as: Growth Hormone Releasing Peptide 2, GHRP2, Pralmorelin, KP-102, GPA-748, GHRP Kaken 100 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic hexapeptide ghrelin-receptor agonist (pralmorelin, KP-102) that raised GH and food intake 36% in healthy men (n=7); approved in Japan as a single-dose GH-deficiency diagnostic (GHRP Kaken 100). GHRP-2 (pralmorelin, KP-102) is a second-generation GHRP from the Bowers series. In children, 1 mcg/kg IV gave a predictable GH rise with a 33 min plasma half-life (Pihoker 1998), and intranasal 5-20 mcg/kg was active (Pihoker 1995). Six GH-deficient children treated SC for 8 months grew faster, though IGF-1 did not rise and the effect of each injection was brief (Mericq 1998). In older adults, 30 days of continuous SC infusion at 1 mcg/kg/h sustained GH secretion at 1.8-fold and raised IGF-1 to a stable plateau (Bowers 2004). A 270 min SC infusion increased ad libitum food intake 36% in healthy men (Laferrere 2005). In Japan a 100 mcg IV test with a 15 mcg/L GH cut-off diagnoses severe adult GH deficiency (Chihara 2007) and it is approved there as a diagnostic. US development was discontinued. No body-composition or sleep trial exists. ### Benefits Sustained GH and IGF-1 elevation over 30 days of SC infusion (human, older adults, n=17), increased food intake (human, n=7), validated GH-deficiency diagnostic (human, approved in Japan), growth velocity in GH-deficient children (human, n=6, open label) ### Dosing reference - Research dose: 1 mcg/kg IV or 100 mcg IV fixed dose (diagnostic); 1 mcg/kg/h SC infusion (30-day study); 0.3-3 mcg/kg/day SC in children; research-community range 100-300 mcg SC 1-3x daily - Range: 100 to 300 mcg, 2-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg IV bolus in diagnostic use, SC injection or infusion in research. GH peaks within 60 min and the GH effect of a single SC dose is brief (Chihara 2007; Mericq 1998). GHRP-2 raised ACTH and cortisol in swine where ipamorelin did not (Raun 1998). Continuous 30-day SC infusion in older adults kept safety screening tests normal (Bowers 2004). ### Mechanism GHRP-2 is an agonist at the ghrelin receptor GHS-R1a on pituitary somatotrophs and in the hypothalamus. It releases GH through a pathway distinct from GHRH, and the two synergize in children and adults (Pihoker 1995; Bowers 2004). Like ghrelin it increases food intake in humans (Laferrere 2005). It also stimulates ACTH and cortisol release (Raun 1998, swine), which ipamorelin does not. GH responses are lower in GH-deficient patients than in healthy subjects regardless of age or adiposity, the basis of its diagnostic use (Chihara 2007). ### Evidence Clinical: at least one published human trial or an approved drug - 1 mcg/kg IV: predictable GH rise, plasma half-life 33 min, in 10 children (Pihoker et al., 1998) - Intranasal 5-20 mcg/kg released GH in children; IV GHRP-2 + GHRH was synergistic (Pihoker et al., 1995) - 8 months of SC 0.3-3 mcg/kg/day raised growth velocity in 6 GH-deficient children without raising IGF-1 (Mericq et al., 1998) - 30-day continuous SC infusion at 1 mcg/kg/h sustained GH secretion and IGF-1 in 17 older adults (Bowers et al., 2004) - SC infusion increased ad libitum food intake 36% in 7 healthy men (Laferrere et al., 2005) - Human-trial status: approved in Japan as a GH-deficiency diagnostic (100 mcg IV, 15 mcg/L cut-off; Chihara et al., 2007); US development discontinued; no approved therapeutic use ### References - [Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. Laferrere B, Abraham C, Russell CD, Bowers CY, Journal of Clinical Endocrinology & Metabolism, 2005](https://doi.org/10.1210/jc.2004-1719) - [Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. Bowers CY, Granda R, Mohan S, Kuipers J, Baylink D, Veldhuis JD, Journal of Clinical Endocrinology & Metabolism, 2004](https://doi.org/10.1210/jc.2003-031799) - [A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Chihara K, Shimatsu A, Hizuka N, Tanaka T, Seino Y, Kato Y; KP-102 Study Group, European Journal of Endocrinology, 2007](https://doi.org/10.1530/EJE-07-0066) - [Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children. Pihoker C, Kearns GL, French D, Bowers CY, Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.4.4744) - [Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature. Pihoker C, Middleton R, Reynolds GA, Bowers CY, Badger TM, Journal of Clinical Endocrinology & Metabolism, 1995](https://doi.org/10.1210/jcem.80.10.7559885) - [Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children. Mericq V, Cassorla F, Bowers CY, Avila A, Gonen B, Merriam GR, Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.7.4969) - [Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN. Adis R&D Profile, Drugs in R&D, 2004](https://pubmed.ncbi.nlm.nih.gov/15230633/) - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) ### Side effects No side effects or toxicities were observed over 8 months in GH-deficient children (Mericq 1998) and safety tests stayed normal over a 30-day infusion in older adults (Bowers 2004). Increased food intake is a documented human effect (Laferrere 2005). ACTH and cortisol rise acutely (Raun 1998, swine). Water retention, tingling in the hands, joint aches and reduced insulin sensitivity are commonly reported (anecdotal). Regulatory: GHRP-2 (injectable and nasal) is on FDA's 503B category 2 (significant safety risks) table, added 2023-09-29, page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~33 min (t1/2 beta; children, IV bolus; Pihoker 1998) - Bioavailability: Intranasal: GH response at 5-20 mcg/kg in children (Pihoker 1995); no absolute bioavailability figure located - Molecular weight: 817.96 Da - Sequence: [D-A][D-2-Nal]AW[D-F]K[NH2] ### Stacks with - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## GHRP-6 URL: https://peptidelabs.app/peptides/ghrp-6/ Also known as: Growth Hormone Releasing Peptide 6, GHRP6, SKF-110679 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview First synthetic GH-releasing hexapeptide (Bowers 1984); raised GH dose-dependently and synergized with GHRH in normal men (n=18). Appetite and gut-motility effects are documented in rodents. GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is the first synthetic growth hormone-releasing peptide, described by Bowers in 1984 before its receptor (GHS-R1a) or its natural ligand ghrelin were known. In normal men, IV doses of 0.1-1 mcg/kg raised peak GH from 1 to 69 mcg/L and acted synergistically with GHRH; prolactin and cortisol roughly doubled at the 1 mcg/kg dose (Bowers 1990, n=18). GHRH plus GHRP-6 became a diagnostic stimulus whose GH response is preserved into old age (Micic 1998). Cuban groups report tissue-protective effects: a 400 mcg/kg dose cut infarct mass 78% in pigs (Berlanga 2007), and GHRP-6 combined with EGF was safe in a phase 1/2 randomized open-label stroke trial (Hernandez-Bernal 2024, n=36). Human PK exists for IV dosing (Cabrales 2013). It is not approved as a drug in any jurisdiction. ### Benefits GH release and GHRH synergy (human, n=18), reduced myocardial infarct size (pig), safety and functional signal in acute stroke with EGF (human phase 1/2, n=36, open label), bone mineral content (rat), food intake and gut transit (rat) ### Dosing reference - Research dose: 0.1-1 mcg/kg IV in human GH studies (about 70 mcg at 1 mcg/kg); 90 mcg IV in the GHRH+GHRP-6 test; research-community range 100-300 mcg SC 1-3x daily - Range: 100 to 300 mcg, 2-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Subcutaneous or IV in research; human GH studies used IV bolus. GH peak occurs within about 30 min. Prolactin and cortisol rose about 2-fold at 1 mcg/kg IV in men (Bowers 1990). Elimination half-life after IV bolus is about 2.5 h (Cabrales 2013). ### Mechanism GHRP-6 is an agonist at the growth hormone secretagogue receptor GHS-R1a, the receptor later found to bind ghrelin (Kojima 1999). It releases GH from pituitary somatotrophs by a pathway separate from GHRH, and the two stimuli synergize in men (Bowers 1990). At 1 mcg/kg IV it also roughly doubled prolactin and cortisol in men (Bowers 1990). In the heart, GHRPs bind CD36 as well as GHS-R1a; CD36 mediates the coronary effects of hexarelin in mice and is a proposed mechanism for the GHRP-6 cardioprotection seen in pigs (Berlanga 2007). ### Evidence Clinical: at least one published human trial or an approved drug - Raised peak GH from 1 to 69 mcg/L at 1 mcg/kg IV and synergized with GHRH in normal men, n=18 (Bowers et al., 1990) - GHRH + GHRP-6 (90 mcg each, IV) produced a preserved GH response in subjects aged 19-96 (Micic et al., 1998) - IV bolus 100-400 mcg/kg: distribution half-life 7.6 min, elimination half-life 2.5 h in nine healthy men (Cabrales et al., 2013) - 400 mcg/kg reduced infarct mass 78% after coronary occlusion in pigs (Berlanga et al., 2007) - EGF + GHRP-6 (3.5-5 mg IV twice daily, 7 days) was safe in a phase 1/2 randomized open-label stroke trial, n=36 (Hernandez-Bernal et al., 2024) - Human-trial status: decades of acute human GH studies and one phase 1/2 combination trial; not approved anywhere ### References - [On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Bowers CY, Momany FA, Reynolds GA, Hong A, Endocrinology, 1984](https://doi.org/10.1210/endo-114-5-1537) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) - [Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers. Cabrales A, Gil J, Fernandez E, et al., European Journal of Pharmaceutical Sciences, 2013](https://doi.org/10.1016/j.ejps.2012.10.006) - [Preserved growth hormone (GH) secretion in aged and very old subjects after testing with the combined stimulus GH-releasing hormone plus GH-releasing hexapeptide-6. Micic D, Popovic V, Doknic M, et al., Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.7.4957) - [Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction. Berlanga J, Cibrian D, Guevara L, et al., Clinical Science (London), 2007](https://doi.org/10.1042/CS20060103) - [Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial. Hernandez-Bernal F, Estenoz-Garcia D, Gutierrez-Ronquillo JH, et al., Frontiers in Neurology, 2024](https://doi.org/10.3389/fneur.2024.1303402) - [The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. Svensson J, Lall S, Dickson SL, et al., Journal of Endocrinology, 2000](https://doi.org/10.1677/joe.0.1650569) - [Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K, Nature, 1999](https://doi.org/10.1038/45230) ### Side effects In men, 1 mcg/kg IV produced no adverse clinical effects; prolactin and cortisol rose about 2-fold at that dose (Bowers 1990). Adverse events in the stroke trial did not exceed control (Hernandez-Bernal 2024). Appetite increase, water retention, tingling in the hands, lethargy and reduced insulin sensitivity are commonly reported (anecdotal) with repeated SC use. Regulatory: GHRP-6 is on FDA's 503B category 2 (significant safety risks) table, added 2023-09-29, page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~2.5 h elimination, 7.6 min distribution (human, IV bolus; Cabrales 2013) - Molecular weight: 873.01 Da - Sequence: H[D-W]AW[D-F]K[NH2] ### Stacks with - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Glutathione URL: https://peptidelabs.app/peptides/glutathione/ Also known as: GSH, L-Glutathione, Reduced glutathione, γ-L-glutamyl-L-cysteinyl-glycine Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Endogenous tripeptide (Glu-Cys-Gly) and the main intracellular antioxidant, central to phase II detoxification and cellular redox defence. Glutathione is the endogenous tripeptide gamma-Glu-Cys-Gly (PubChem CID 124886), the main intracellular thiol antioxidant. The human trial record is mixed and route-dependent. Oral dosing at 250 or 1000 mg/day for 6 months raised glutathione in blood, erythrocytes, plasma, lymphocytes and buccal cells in 54 adults, with stores returning to baseline a month after stopping (Richie 2015). Oral 500 mg/day for 4 weeks lowered melanin index at 2 of 6 measured sites in 60 subjects (Arjinpathana 2012). By injection the picture is worse: a randomized trial of intravenous glutathione 1400 mg three times weekly for 4 weeks in 21 Parkinson patients found no significant UPDRS difference (Hauser 2009), and intranasal dosing was not superior to placebo (Mischley 2017). No parenteral glutathione product is approved for any systemic or cosmetic indication. ### Benefits Raised blood, erythrocyte and lymphocyte glutathione stores and lowered the oxidized to reduced ratio at 250 to 1000 mg/day oral for 6 months (human RCT, n=54), lower melanin index at 500 mg/day oral for 4 weeks (human RCT, n=60), phase II detoxification cofactor (biochemistry, not a trial) ### Dosing reference - Research dose: 200 to 600 mg by injection: clinic and community range. Published intravenous doses were higher: 1400 mg three times weekly (Hauser 2009) and 600 mg twice daily for 30 days (Sechi 1996) - Range: 200000 to 600000 mcg, 1-3x weekly - Reconstitution: 5 mL bacteriostatic water - Common vial sizes: 200 mg, 600 mg Intravenous or subcutaneous in research and clinic use. Published human doses, verbatim: 1400 mg intravenously three times a week for 4 weeks, randomized and placebo-controlled, no significant effect (Hauser 2009); 600 mg intravenously twice daily for 30 days, open label, 42% decline in disability (Sechi 1996); 100 or 200 mg intranasally three times daily for 3 months, not superior to placebo (Mischley 2017); 250 to 1000 mg/day orally for 6 months, which raised body stores (Richie 2015). No parenteral product is approved for a cosmetic indication anywhere, and compounded sterility is a documented problem. ### Mechanism Glutathione cycles between its reduced (GSH) and oxidized (GSSG) forms, serves as the cofactor for glutathione peroxidases, and is conjugated to electrophiles by glutathione-S-transferases for phase II elimination. The skin-lightening rationale is inhibition of tyrosinase and a shift from eumelanin to pheomelanin, which is in vitro pharmacology rather than a demonstrated mechanism in treated skin (Dlova 2026). One mechanistic claim in the old record is wrong in the other direction: parenteral dosing is justified by poor oral absorption, yet the one long randomized oral trial raised body stores at 250 and 1000 mg/day (Richie 2015), and liposomal oral dosing raised stores and natural killer activity (Sinha 2018). Direct cellular uptake of intact glutathione is limited; the gamma-glutamyl cycle normally breaks it down extracellularly and reassembles it inside cells. ### Evidence Clinical: at least one published human trial or an approved drug - Oral glutathione at 250 or 1000 mg/day for 6 months raised glutathione in blood, erythrocytes, plasma, lymphocytes and buccal cells in 54 adults, lowered the oxidized to reduced ratio, and more than doubled natural killer cytotoxicity in the high-dose group; levels returned to baseline after a 1-month washout (Richie et al., 2015) - Oral 500 mg/day for 4 weeks lowered melanin index at all six measured sites in 60 healthy subjects, reaching significance versus placebo at two sites (Arjinpathana et al., 2012) - Intravenous glutathione 1400 mg three times weekly for 4 weeks in 21 Parkinson patients was well tolerated but produced no significant UPDRS difference; a 2.8-unit mean improvement did not reach significance and reversed during follow-up (Hauser et al., 2009) - An earlier open-label series of 9 untreated early Parkinson patients given 600 mg intravenously twice daily for 30 days reported a 42% decline in disability lasting 2 to 4 months after stopping, with no control group (Sechi et al., 1996) - Intranasal glutathione at 100 or 200 mg three times daily for 3 months in 45 Parkinson patients improved UPDRS scores, but so did placebo, and neither dose separated from it; one high-dose participant developed cardiomyopathy (Mischley et al., 2017) - Human-trial status: the positive randomized evidence is oral. No randomized trial of injected glutathione has shown benefit for any indication, and a 2026 scoping review of systemic glutathione for skin lightening found the intravenous evidence base inadequate. The only US-approved product containing glutathione is an intraocular irrigating solution, BSS PLUS (NDA 018469) ### References - [Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Richie JP Jr, Nichenametla S, Neidig W, Calcagnotto A, et al., European Journal of Nutrition, 2015](https://doi.org/10.1007/s00394-014-0706-z) - [Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study. Arjinpathana N, Asawanonda P, Journal of Dermatological Treatment, 2012](https://doi.org/10.3109/09546631003801619) - [Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D, Movement Disorders, 2009](https://doi.org/10.1002/mds.22401) - [Reduced intravenous glutathione in the treatment of early Parkinson's disease. Sechi G, Deledda MG, Bua G, Satta WM, et al., Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1996](https://doi.org/10.1016/s0278-5846(96)00103-0) - [Phase IIb Study of Intranasal Glutathione in Parkinson's Disease. Mischley LK, Lau RC, Shankland EG, Wilbur TK, Padowski JM, Journal of Parkinson's Disease, 2017](https://doi.org/10.3233/JPD-161040) - [Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Sinha R, Sinha I, Calcagnotto A, Trushin N, et al., European Journal of Clinical Nutrition, 2018](https://doi.org/10.1038/ejcn.2017.132) - [Systemic glutathione for skin lightening: a scoping review of current evidence. Dlova NC, Enechukwu NA, Cole-Adeife O, Sagoe D, Journal of the European Academy of Dermatology and Venereology, 2026](https://doi.org/10.1111/jdv.70514) - [Glutathione Whitening Pills Induced Toxic Epidermal Necrolysis: An Unusual Case Confirmed by Enzyme-Linked Immunospot Assay and Liquid Chromatography-Mass Spectrometry. Chottawornsak N, Tansrisawad N, Tubtimrattana A, Thantiworasit P, et al., Dermatitis, 2022](https://doi.org/10.1097/DER.0000000000000782) ### Side effects In the randomized trials glutathione was well tolerated: adverse events matched placebo at 1400 mg intravenously three times weekly (Hauser 2009) and at 250 to 1000 mg/day orally for 6 months (Richie 2015). Serious harms are documented in case reports and reviews of cosmetic use rather than in trials: toxic epidermal necrolysis after glutathione whitening pills, confirmed by ELISpot and mass spectrometry (Chottawornsak 2022), systemic inflammatory response syndrome after a high-dose intravenous glutathione revitalizing solution, reported as a single case in 2025, and one cardiomyopathy case in the intranasal trial. A 2026 scoping review concludes that the systemic skin-lightening evidence does not support the practice. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not reported in the published human trials. Oral dosing at 250 to 1000 mg/day for 6 months raised body stores, which returned to baseline within a 1-month washout (Richie 2015) - Bioavailability: Oral: absolute bioavailability has not been measured, but 250 to 1000 mg/day for 6 months raised blood, erythrocyte, plasma and lymphocyte stores (Richie 2015), and liposomal oral dosing raised stores and immune markers (Sinha 2018). Injection: no bioavailability or exposure data from the published trials - Molecular weight: 307.33 Da - Sequence: γ-Glu-Cys-Gly (γ-glutamyl bond, not standard peptide bond) ### Stacks with - [NAD+](https://peptidelabs.app/peptides/nad/) - [NMN](https://peptidelabs.app/peptides/nmn/) ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Immune](https://peptidelabs.app/peptides/category/immune/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Gonadorelin (GnRH) URL: https://peptidelabs.app/peptides/gonadorelin-gnrh/ Also known as: GnRH, LHRH, Luteinizing hormone-releasing hormone, Factrel, Lutrepulse, Gonadorelin acetate, Gonadorelin hydrochloride, Cystorelin (veterinary), Fertagyl (veterinary) Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic GnRH decapeptide; pulsatile doses raise LH and FSH, continuous exposure suppresses them. US human products Factrel (1982) and Lutrepulse (1989) are discontinued. Gonadorelin is synthetic gonadotropin-releasing hormone, identical to the hypothalamic decapeptide. The FDA approved it as Factrel (NDA 018123, 1982) for testing pituitary gonadotropin reserve and as Lutrepulse (NDA 019687, 1989) for pulsatile pump induction of ovulation; both are discontinued. Every current gonadorelin label on DailyMed is veterinary (Factrel by Zoetis, Cystorelin, Fertagyl, used in cattle). Human trials used an infusion pump giving a pulse every 1 to 2 hours, which induced puberty in men and ovulation in women with hypogonadotropic hypogonadism (Hoffman 1982; Martin 1993). The once-daily subcutaneous use alongside TRT sold by vendors has no published trial. ### Benefits LH and FSH release test of pituitary reserve (approved diagnostic, US product discontinued), puberty and ovulation induction by pulsatile pump in hypogonadotropic hypogonadism (human trials), testicular support during TRT (community use, no trial) ### Dosing reference - Research dose: Community range 200 to 300 mcg subcutaneous (off-label; no current US human label). - Range: 200 to 300 mcg, 1x daily (before bed) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Community protocols use 200 to 300 mcg subcutaneously to stimulate LH and FSH alongside TRT (off-label). The US human products Factrel and Lutrepulse are discontinued, so no current label gives a dose. Sustained exposure suppresses the gonadal axis rather than stimulating it. ### Mechanism Gonadorelin binds the GnRH receptor on pituitary gonadotrophs and releases LH and FSH (Conn 1991). The response depends on the pattern of exposure: in rhesus monkeys with hypothalamic lesions, hourly pulses restored LH and FSH secretion while a continuous infusion of the same hormone suppressed it (Belchetz 1978). That finding is the basis both for pulsatile pump therapy and for long-acting GnRH agonists used to shut the axis down. Native GnRH is cleared within minutes, which is why therapeutic use needed a pump rather than daily injections (Handelsman 1986). ### Evidence Clinical: at least one published human trial or an approved drug - Hourly GnRH pulses restored LH and FSH in rhesus monkeys with hypothalamic lesions, while continuous infusion suppressed them (Belchetz et al., 1978) - Long-term low-dose pulsatile GnRH induced puberty in men with hypogonadotropic hypogonadism (Hoffman and Crowley, 1982) - Pulsatile GnRH was compared with exogenous gonadotropins for ovulation induction in women with hypogonadotropic amenorrhea (Martin et al., 1993) - Review of GnRH and its analogue pharmacology in reproductive medicine (Conn and Crowley, 1991) - Human-trial status: approved by the FDA as Factrel (1982, diagnostic) and Lutrepulse (1989, ovulation induction), both discontinued; current US labels are veterinary only, and no trial has tested daily subcutaneous gonadorelin during TRT ### References - [Gonadotropin-releasing hormone and its analogues. Conn PM, Crowley WF Jr, New England Journal of Medicine, 1991](https://doi.org/10.1056/NEJM199101103240205) - [Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Belchetz PE, Plant TM, Nakai Y, et al., Science, 1978](https://doi.org/10.1126/science.100883) - [Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone. Hoffman AR, Crowley WF Jr, New England Journal of Medicine, 1982](https://doi.org/10.1056/NEJM198211113072003) - [Comparison of exogenous gonadotropins and pulsatile gonadotropin-releasing hormone for induction of ovulation in hypogonadotropic amenorrhea. Martin KA, Hall JE, Adams JM, Crowley WF Jr, Journal of Clinical Endocrinology & Metabolism, 1993](https://doi.org/10.1210/jcem.77.1.8325934) - [Pharmacokinetics of gonadotropin-releasing hormone and its analogs. Handelsman DJ, Swerdloff RS, Endocrine Reviews, 1986](https://doi.org/10.1210/edrv-7-1-95) ### Side effects Injection-site reactions, headache, nausea, and flushing are the most common effects. Continuous rather than pulsatile administration downregulates the pituitary and suppresses the gonadal axis, the opposite of the intended effect. Rare hypersensitivity reactions have been reported. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~2-4 minutes (very short) - Bioavailability: Subcutaneous: Rapid absorption; requires frequent pulsatile dosing for physiologic effect - Molecular weight: 1182.29 Da - Sequence: pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 ### Stacks with - [Kisspeptin-10](https://peptidelabs.app/peptides/kisspeptin-10/) - [HCG](https://peptidelabs.app/peptides/hcg/) ### Categories - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) - [Fertility](https://peptidelabs.app/peptides/category/fertility/) ## GW501516 URL: https://peptidelabs.app/peptides/gw501516/ Also known as: Cardarine, GW-501516, Endurobol, GSK-516 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Small-molecule PPAR-delta agonist (Cardarine), not a peptide. Raised HDL and lowered LDL and triglycerides in 2 to 12 week human trials; development stopped after rodent studies found tumours at all doses. GW501516 is a selective PPAR-delta agonist from GlaxoSmithKline, described in 2003 (Sznaidman). In obese rhesus monkeys it raised HDL and lowered triglycerides and insulin (Oliver 2001). In healthy volunteers, 2.5 or 10 mg daily for 2 weeks raised HDL (Sprecher 2007); in moderately obese men, 10 mg daily for 2 weeks lowered triglycerides, LDL, insulin and liver fat and raised fat oxidation (Risérus 2008). A 12-week phase 2 trial in 268 people with low HDL found HDL up to 16.9% higher at 10 mg (Olson 2012). In mice it raised running endurance with exercise (Narkar 2008). Two-year GSK studies found treatment-related tumours in many tissues in rats and mice at every dose, and development was halted. WADA has prohibited it since 2009 and issued a health warning in 2013. No trial is active. ### Benefits Raised HDL cholesterol and lowered LDL, triglycerides and apoB (human RCTs, 2 to 12 weeks), increased fat oxidation and lowered liver fat (human, 2 weeks, n=6 per arm), running endurance (mouse) ### Dosing reference - Research dose: 2.5 to 10 mg once daily by mouth (doses used in 2 to 12 week human trials; development halted for rodent carcinogenicity) - Range: 2500 to 10000 mcg, 1x daily Oral. Human trials used 2.5, 5 or 10 mg once daily for 2 weeks (Sprecher 2007; Risérus 2008) or 12 weeks (Olson 2012). Rodent carcinogenicity studies dosed 3 to 80 mg/kg/day for 104 weeks and found tumours at every dose. No long-term human dosing has been studied. ### Mechanism GW501516 binds and activates PPAR-delta (PPARβ/δ), a nuclear receptor, with high selectivity over PPAR-alpha and PPAR-gamma (Sznaidman 2003). In human skeletal muscle cells it raised fatty acid oxidation and expression of CPT1, CD36 and the cholesterol efflux transporter ABCA1 (Sprecher 2007). In obese men it raised the share of dietary fat oxidised and muscle CPT1b expression (Risérus 2008). In primates, ABCA1 induction is the proposed basis of the HDL rise (Oliver 2001). In mice, combined with exercise, it induced oxidative muscle gene programmes (Narkar 2008). PPAR-delta activation also accelerated intestinal adenoma growth in Apc(min) mice, which is the proposed link to the rodent tumour findings (Gupta 2004). ### Evidence Clinical: at least one published human trial or an approved drug - 12 weeks of 2.5 to 10 mg daily in 268 people with low HDL raised HDL up to 16.9% and lowered LDL 7.3% and triglycerides 16.9% (Olson et al., 2012) - 10 mg daily for 2 weeks in moderately obese men lowered triglycerides 30%, LDL 23%, insulin 11% and liver fat 20%, and raised fat oxidation (Risérus et al., 2008) - First human report: 2.5 or 10 mg daily for 2 weeks raised HDL in healthy volunteers (Sprecher et al., 2007) - Raised running endurance in exercised mice; with AICAR it was the original 'exercise mimetic' paper (Narkar et al., 2008) - Increased the number and size of intestinal polyps in Apc(min) mice (Gupta et al., 2004); 104-week GSK studies found tumours in many tissues in rats and mice at all doses (Geiger and Newsholme, Toxicologist 2009) - Human-trial status: development halted after the rodent carcinogenicity findings; no active trials; WADA-prohibited since 2009 ### References - [Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity. Sznaidman ML, Haffner CD, Maloney PR, et al., Bioorganic & Medicinal Chemistry Letters, 2003](https://doi.org/10.1016/s0960-894x(03)00207-5) - [A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Oliver WR Jr, Shenk JL, Snaith MR, et al., Proceedings of the National Academy of Sciences of the United States of America, 2001](https://doi.org/10.1073/pnas.091021198) - [Triglyceride:high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor delta agonist. Sprecher DL, Massien C, Pearce G, et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2007](https://doi.org/10.1161/01.ATV.0000252790.70572.0c) - [Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men. Risérus U, Sprecher D, Johnson T, et al., Diabetes, 2008](https://doi.org/10.2337/db07-1318) - [Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome. Olson EJ, Pearce GL, Jones NP, Sprecher DL, Arteriosclerosis, Thrombosis, and Vascular Biology, 2012](https://doi.org/10.1161/ATVBAHA.112.247890) - [AMPK and PPARdelta agonists are exercise mimetics. Narkar VA, Downes M, Yu RT, et al., Cell, 2008](https://doi.org/10.1016/j.cell.2008.06.051) - [Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Gupta RA, Wang D, Katkuri S, et al., Nature Medicine, 2004](https://doi.org/10.1038/nm993) - [Metabolic modulators of the exercise response: doping control analysis of an agonist of the peroxisome proliferator-activated receptor δ (GW501516) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Pokrywka A, Cholbinski P, Kaliszewski P, et al., Journal of Physiology and Pharmacology, 2014](https://pubmed.ncbi.nlm.nih.gov/25179079/) ### Side effects Published human trials (2 to 12 weeks, up to 10 mg daily) report lipid outcomes and no serious drug-related findings, but none ran long enough to address cancer risk. In 104-week GSK studies, rats given 3 to 40 mg/kg/day developed treatment-related tumours in liver, bladder, thyroid, stomach, tongue, skin, uterus and other tissues, with higher mortality in females at all doses; mice given 10 to 80 mg/kg/day developed liver and squamous stomach tumours. It enlarged intestinal polyps in Apc(min) mice. WADA issued a public health warning in 2013. No long-term human safety data exist. ### Storage - Storage: Room temperature, dry, protected from light (general small-molecule guidance; no compound-specific CoA located) - Lyophilized: 24+ months ### Pharmacology - Half-life: Not reported in peer-reviewed literature; human trials dosed once daily by mouth (Sprecher 2007; Olson 2012) - Bioavailability: Orally active in rodents, primates and humans (Oliver 2001; Sprecher 2007); no absolute bioavailability figure published - Molecular weight: 453.5 Da ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## HCG URL: https://peptidelabs.app/peptides/hcg/ Also known as: Human Chorionic Gonadotropin, hCG, Chorionic gonadotropin, Pregnyl, Novarel Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Urine-derived placental glycoprotein acting on the LH receptor; labeled IM as Pregnyl and Novarel for cryptorchidism, male hypogonadotropic hypogonadism and ovulation induction. TRT use is off-label. Human chorionic gonadotropin is a placental glycoprotein of an alpha subunit shared with LH, FSH and TSH and a hormone-specific beta subunit. Urine-derived hCG is marketed in the US as Pregnyl (BLA 017692, 1976) and Novarel (BLA 017016, 1974), both intramuscular only, for prepubertal cryptorchidism, selected men with hypogonadotropic hypogonadism, and ovulation induction after gonadotropin pretreatment. Both labels state that hCG has not been shown to help obesity, and a meta-analysis of the Simeons diet trials agreed (Lijesen 1995). Use alongside testosterone therapy rests on a small study showing preserved intratesticular testosterone (Coviello 2005) and is off-label. Vendor research vials are not the labeled products. ### Benefits Leydig-cell testosterone and spermatogenesis support in male hypogonadotropic hypogonadism (FDA-labeled), ovulation trigger (FDA-labeled), intratesticular testosterone maintained during TRT (small human study, off-label), no effect on obesity (label, meta-analysis) ### Dosing reference - Research dose: Community range 250 to 500 IU 2 to 3 times weekly alongside TRT (off-label). Label regimens are in the dosing notes. - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5000 mg, 10000 mg Label regimen for selected men with hypogonadotropic hypogonadism (Pregnyl, Novarel), IM only: 500 to 1,000 USP units 3 times a week for 3 weeks, then the same dose twice a week for 3 weeks; or 4,000 USP units 3 times weekly for 6 to 9 months, then 2,000 USP units 3 times weekly for 3 more months. The 250 to 500 IU 2 to 3x weekly range in this record is off-label use alongside TRT; Coviello 2005 tested low doses every other day in healthy men. ### Mechanism hCG acts at the LH/CG receptor with an action the labels describe as virtually identical to pituitary LH, plus a small degree of FSH activity. In the testis it stimulates Leydig cells to make androgens, which can bring about testicular descent where no anatomical block exists; in the ovary it can stand in for the mid-cycle LH surge to trigger ovulation and maintains the corpus luteum (Pregnyl and Novarel labels). In healthy men whose LH was suppressed by testosterone enanthate, low-dose hCG kept intratesticular testosterone near baseline (Coviello 2005). The labels state it has no known effect on fat mobilization, appetite or fat distribution. ### Evidence Clinical: at least one published human trial or an approved drug - Low-dose hCG every other day kept intratesticular testosterone near baseline in healthy men on testosterone enanthate (Coviello et al., 2005) - Subcutaneous self-administered FSH plus hCG induced spermatogenesis in men with hypogonadotropic hypogonadism (Burgués et al., 1997) - Meta-analysis of hormonal treatment of cryptorchidism, including hCG, found modest descent rates (Pyörälä et al., 1995) - Criteria-based meta-analysis of hCG with the Simeons diet found no evidence of added weight loss (Lijesen et al., 1995) - Human-trial status: urinary hCG is approved by the FDA and marketed as Pregnyl (BLA 017692) and Novarel (BLA 017016), IM only; TRT co-therapy is off-label ### References - [Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. Coviello AD et al, Journal of Clinical Endocrinology & Metabolism, 2005](https://doi.org/10.1210/jc.2004-0802) - [The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. Lijesen GK, Theeuwen I, Assendelft WJ, Van Der Wal G, British Journal of Clinical Pharmacology, 1995](https://doi.org/10.1111/j.1365-2125.1995.tb05779.x) - [A review and meta-analysis of hormonal treatment of cryptorchidism. Pyörälä S, Huttunen NP, Uhari M, Journal of Clinical Endocrinology & Metabolism, 1995](https://doi.org/10.1210/jcem.80.9.7673426) - [Subcutaneous self-administration of highly purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism. Spanish Collaborative Group on Male Hypogonadotropic Hypogonadism. Burgués S, Calderón MD, Human Reproduction, 1997](https://doi.org/10.1093/humrep/12.5.980) ### Side effects Labels (Pregnyl, Novarel): headache, irritability, restlessness, depression, fatigue, edema, gynecomastia, precocious puberty in boys treated for cryptorchidism, injection-site pain, and hypersensitivity reactions including anaphylaxis. With gonadotropin ovulation induction: ovarian hyperstimulation syndrome, ovarian cyst enlargement or rupture, multiple births and arterial thromboembolism. The benzyl alcohol diluent is not for use in newborns. ### Storage - Storage: Powder: room temperature, 20 to 25°C (Novarel) or 15 to 25°C (Pregnyl); refrigerate 2 to 8°C after reconstitution - Lyophilized: 24+ months at room temperature - Reconstituted: 30 days refrigerated (Novarel) or 60 days (Pregnyl) ### Pharmacology - Half-life: Urinary hCG labels give no half-life. Recombinant hCG (Ovidrel): terminal 29 ± 6 h after 250 mcg SC in healthy women, initial IV phase 4.5 h (Ovidrel label) - Bioavailability: Pregnyl and Novarel are labeled for IM use only. SC absolute bioavailability of recombinant hCG is about 40% in women (Ovidrel label); no SC figure is labeled for urinary hCG. - Molecular weight: 36000 Da ### Stacks with - [Gonadorelin (GnRH)](https://peptidelabs.app/peptides/gonadorelin-gnrh/) - [Kisspeptin-10](https://peptidelabs.app/peptides/kisspeptin-10/) ### Categories - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) - [Fertility](https://peptidelabs.app/peptides/category/fertility/) - [Sexual Health](https://peptidelabs.app/peptides/category/sexual-health/) ## Hexarelin URL: https://peptidelabs.app/peptides/hexarelin/ Also known as: Examorelin, EP-23905, MF-6003, Hexarelin acetate Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Highly potent synthetic hexapeptide GH secretagogue that also showed direct cardioprotective effects in animal work; desensitizes the GH axis with continuous use. Hexarelin (examorelin) is a GHRP-6 analog with a methylated D-Trp. In 12 healthy men, 1 mcg/kg IV released about twice the GH of 1 mcg/kg GHRH; it was also active SC (1.5-3 mcg/kg), intranasally and orally (Ghigo 1994). A double-blind rising-dose study put the IV ED50 near 0.5 mcg/kg (Imbimbo 1994). Intranasal 60 mcg/kg three times daily raised growth velocity from 5.3 to 8.3 cm/year in eight short children (Laron 1995). Sixteen weeks of 1.5 mcg/kg SC twice daily in adults produced a partial, reversible blunting of the GH response and no change in IGF-1 or body composition (Rahim 1998). It also has GH-independent cardiac actions: protection of hypophysectomized rat hearts from ischemia-reperfusion (Locatelli 1999) and higher ejection fraction and cardiac output in bypass patients (Broglio 2002, n=24). Not developed as a drug. ### Benefits GH release about 2x that of GHRH (human, n=12), growth velocity in short children (human, n=8, intranasal), cardiac output during bypass surgery (human, n=24), protection from ischemia-reperfusion injury (rat) ### Dosing reference - Research dose: 1-2 mcg/kg IV or 1.5-3 mcg/kg SC in human GH studies (about 100-200 mcg for 70 kg); 1.5 mcg/kg SC 2x daily for 16 weeks in the longest adult trial - Range: 100 to 200 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Subcutaneous in research; human studies used IV, SC, intranasal and oral routes. GH peaks about 30 min after an IV bolus (Imbimbo 1994). With 16 weeks of twice-daily SC dosing the GH response fell by about half by week 4 and recovered within 4 weeks of stopping (Rahim 1998). ### Mechanism Hexarelin is an agonist at the ghrelin receptor GHS-R1a on pituitary somatotrophs and hypothalamic neurons, releasing GH by a pathway independent of GHRH; GHRH co-administration potentiates the response in young and old men (Arvat 1994). Its cardiac effects do not depend on GH: they persist in hypophysectomized rats (Locatelli 1999), and in mice they are mediated by the scavenger receptor CD36, to which hexarelin binds in the heart (Bodart 2002). Chronic exposure partially down-regulates the pituitary GH response, reversibly (Rahim 1998). ### Evidence Clinical: at least one published human trial or an approved drug - 1 mcg/kg IV released about 2x the GH of 1 mcg/kg GHRH in 12 healthy men; SC bioavailability 77% by GH response (Ghigo et al., 1994) - Double-blind rising-dose study: GH peaked at 30 min, ED50 about 0.5 mcg/kg IV (Imbimbo et al., 1994) - Intranasal 60 mcg/kg 3x daily raised growth velocity from 5.3 to 8.3 cm/year in 8 short children (Laron et al., 1995) - 16 weeks of 1.5 mcg/kg SC 2x daily: partial reversible blunting of GH response, no change in IGF-1 or body composition (Rahim et al., 1998) - Acute 2 mcg/kg IV raised ejection fraction and cardiac output in 24 bypass-surgery patients; GHRH and GH did not (Broglio et al., 2002) - Human-trial status: small human physiology studies only; not approved anywhere ### References - [Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. Ghigo E, Arvat E, Gianotti L, et al., Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.78.3.8126144) - [Growth hormone-releasing activity of hexarelin in humans. A dose-response study. Imbimbo BP, Mant T, Edwards M, et al., European Journal of Clinical Pharmacology, 1994](https://doi.org/10.1007/BF00191904) - [Growth hormone status during long-term hexarelin therapy. Rahim A, O'Neill PA, Shalet SM, Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.5.4812) - [Intranasal administration of the GHRP hexarelin accelerates growth in short children. Laron Z, Frenkel J, Deghenghi R, Anin S, Klinger B, Silbergeld A, Clinical Endocrinology (Oxford), 1995](https://doi.org/10.1111/j.1365-2265.1995.tb02929.x) - [Growth hormone-independent cardioprotective effects of hexarelin in the rat. Locatelli V, Rossoni G, Schweiger F, et al., Endocrinology, 1999](https://doi.org/10.1210/endo.140.9.6948) - [Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery. Broglio F, Guarracino F, Benso A, et al., European Journal of Pharmacology, 2002](https://doi.org/10.1016/s0014-2999(02)01934-9) - [CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Bodart V, Febbraio M, Demers A, et al., Circulation Research, 2002](https://doi.org/10.1161/01.res.0000016164.02525.b4) - [Radioimmunoassay for hexarelin, a peptidic growth hormone secretagogue, and its pharmacokinetic studies. Roumi M, Marleau S, du Souich P, et al., Peptides, 1995](https://doi.org/10.1016/0196-9781(95)02022-o) ### Side effects In trials the main finding was a partial, reversible blunting of the GH response after weeks of dosing (Rahim 1998); children treated intranasally for up to 8 months had no reported adverse effects (Laron 1995). Water retention, appetite increase, lethargy, joint aches and reduced insulin sensitivity are commonly reported (anecdotal). ### Storage - Storage: Refrigerated (2-8C) - Lyophilized: 24+ months refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~120 min terminal (dog, IV; Roumi 1995); no human PK located. GH peaks ~30 min after IV bolus in men (Imbimbo 1994) - Bioavailability: SC ~77%, intranasal ~5%, oral ~0.3% (human; GH-response-based estimates, Ghigo 1994) - Molecular weight: 887 Da - Sequence: H[D-2-Me-W]AW[D-F]K[NH2] ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## HMG URL: https://peptidelabs.app/peptides/hmg/ Also known as: Menopur, Pergonal, Humegon, Repronex, Human Menopausal Gonadotropin, Menotropins, hMG Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Urine-derived menotropins with FSH and LH activity; Menopur (2004) is the only marketed US product, labeled for follicle development in IVF. Pergonal, Humegon and Repronex are discontinued. Human menopausal gonadotropin (menotropins) is extracted and purified from the urine of postmenopausal women and carries FSH and LH activity; Menopur vials hold 75 IU of each, and hCG is detectable in the product. Pergonal, the first menotropin, was approved in the US in 1975 and is discontinued, as are Humegon and Repronex. Menopur (BLA 021663, 2004) is the only marketed US menotropin, labeled for development of multiple follicles and pregnancy in ovulatory women as part of assisted reproduction. None of these products is recombinant. Vendor research vials are not the labeled product. ### Benefits Multiple follicle development and pregnancy in women undergoing IVF (FDA-labeled; RCTs non-inferior to recombinant FSH), spermatogenesis induction in men (historic use, not a current US indication) ### Dosing reference - Research dose: Community range 75 to 150 IU daily. The Menopur label regimen (ART in women) is in the dosing notes. - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 75 mg, 150 mg Menopur label (ART in women), SC: starting dose 225 IU per day for the first cycle; adjust after 5 days by no more than 150 IU at a time; no more than 450 IU per day; stimulation up to 20 days in the pivotal trial. The 75 to 150 IU daily range in this record does not match the current US label, and no current US label covers men. ### Mechanism Menotropins supply FSH, which drives growth and maturation of ovarian follicles, and LH activity, which supports follicular steroid production. Given for 7 to 20 days to women without primary ovarian failure, Menopur produces follicular growth and maturation but usually not ovulation; hCG is then needed to trigger it (Menopur label). In men, FSH acts on Sertoli cells to support spermatogenesis and LH on Leydig cells to make testosterone. Menopur and Pergonal are urinary extracts, not recombinant proteins (Menopur label; Lunenfeld 2004). ### Evidence Clinical: at least one published human trial or an approved drug - Highly purified hMG versus recombinant FSH in IVF after GnRH agonist suppression: ongoing pregnancy rates non-inferior (MERIT, Andersen et al., 2006); the label reports 23% continuing pregnancy in 373 Menopur patients - Highly purified hMG versus recombinant FSH in a GnRH antagonist cycle with single-blastocyst transfer (MEGASET, Devroey et al., 2012) - Historical account of urinary gonadotropins from Pergonal onward (Lunenfeld, 2004) - Human-trial status: approved by the FDA as Menopur (BLA 021663, 2004) for multiple follicle development in ART, marketed; Pergonal (1975), Humegon (1994) and Repronex (1999) are discontinued; no current US label covers men ### References - [Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Andersen AN, Devroey P, Arce JC, Human Reproduction, 2006](https://doi.org/10.1093/humrep/del284) - [A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Devroey P, Pellicer A, Nyboe Andersen A, Arce JC, Fertility and Sterility, 2012](https://doi.org/10.1016/j.fertnstert.2011.12.016) - [Historical perspectives in gonadotrophin therapy. Lunenfeld B, Human Reproduction Update, 2004](https://doi.org/10.1093/humupd/dmh044) ### Side effects Menopur label: abdominal pain, cramps and enlargement, headache, injection-site pain and inflammation, and OHSS were the most common. Serious: abnormal ovarian enlargement, ovarian hyperstimulation syndrome, ovarian torsion, atelectasis or respiratory distress, thromboembolic events, multi-fetal gestation, ectopic pregnancy, spontaneous abortion, congenital malformations and ovarian neoplasms. ### Storage - Storage: Powder: 3 to 25°C, refrigerated or room temperature, protected from light (Menopur label) - Lyophilized: 24+ months at room temperature - Reconstituted: Use immediately after reconstitution; discard unused material (Menopur label) ### Pharmacology - Half-life: FSH elimination half-life 11 to 13 h after multiple SC or IM doses in pituitary-suppressed women (Menopur label); LH half-life not reported - Bioavailability: SC trends toward higher exposure than IM: single 225 IU dose FSH AUC 726 vs 656 h·mIU/mL in 33 healthy women (Menopur label). Absolute bioavailability not reported. ### Stacks with - [Gonadorelin (GnRH)](https://peptidelabs.app/peptides/gonadorelin-gnrh/) - [HCG](https://peptidelabs.app/peptides/hcg/) ### Categories - [Fertility](https://peptidelabs.app/peptides/category/fertility/) - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) ## Humanin URL: https://peptidelabs.app/peptides/humanin/ Also known as: HN, MT-RNR2 peptide, HNG (S14G-humanin analog) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview 24-amino-acid peptide encoded within mitochondrial DNA that protected neurons and other cells from oxidative and apoptotic stress in animal and cell studies. Humanin is a 24-amino acid peptide encoded in mitochondrial DNA. It was originally discovered as a neuroprotective factor against Alzheimer's disease. Research shows broad cytoprotective effects including protection against oxidative stress, apoptosis, and age-related cellular decline. Studies indicate roles in metabolic regulation, cardiovascular protection, and longevity pathways. ### Benefits Neuroprotection against amyloid-beta toxicity (cell culture), insulin sensitisation and cardioprotection (rodent, mostly via the HNG analog), lifespan extension (C. elegans); human data are observational only ### Dosing reference - Research dose: 1 to 5 mg daily (community range, no published human dose; animal work used the HNG analog at milligram-per-kilogram doses by intraperitoneal or intracerebroventricular routes) - Range: 1000 to 5000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Subcutaneous injection is community practice. No human dosing study exists in any indication. Published animal dosing is weight-based and by other routes: HNG at 2 mg/kg intraperitoneally in the mouse ischaemia-reperfusion model (Muzumdar et al., 2010), continuous intracerebroventricular infusion and intravenous analog in rats (Muzumdar et al., 2009), and twice-weekly HNG in middle-aged mice (Yen et al., 2020). Most in vivo results belong to HNG, which is more potent than the native peptide. ### Mechanism Humanin is a 24-residue peptide encoded in the 16S rRNA region of mitochondrial DNA, found by expression screening for factors that block neuronal death caused by familial Alzheimer genes and amyloid-beta (Hashimoto et al., 2001). It binds Bax and keeps it from translocating to mitochondria, which is how it suppresses apoptosis (Guo et al., 2003), and it also binds and blocks Bid and BimEL. Central infusion improved insulin sensitivity in rats through hypothalamic STAT-3; blocking hypothalamic STAT-3 removed the liver effect, and the peptide had no direct effect on isolated hepatocytes (Muzumdar et al., 2009). Cardioprotection in mice ran through AMPK and endothelial nitric oxide synthase phosphorylation (Muzumdar et al., 2010). Note that most in vivo work used the more potent analog HNG (S14G-humanin), not the native peptide. ### Evidence Preclinical: animal or in vitro data only - Identified by expression screening as a factor that abolishes neuronal death caused by multiple familial Alzheimer's disease genes and by amyloid-beta in cell culture (Hashimoto et al., 2001) - Suppresses apoptosis by interfering with Bax activation (Guo et al., 2003) - Intracerebroventricular infusion improved whole-body insulin sensitivity in rats via hypothalamic STAT-3, and an intravenous analog lowered blood glucose in Zucker diabetic fatty rats (Muzumdar et al., 2009) - The analog HNG given intraperitoneally before or at reperfusion reduced infarct size and improved ejection fraction in a mouse coronary occlusion model, best at 2 mg/kg (Muzumdar et al., 2010) - Overexpression extended lifespan in C. elegans, and twice-weekly HNG in middle-aged mice improved metabolic healthspan markers; circulating levels were higher in children of centenarians than age-matched controls (Yen et al., 2020) - Human-trial status: no interventional trial of humanin exists. Human data are observational: lower circulating humanin in coronary artery disease, prognostic for cardiac events (Cai et al., 2022), and higher skeletal muscle humanin after resistance training in men with impaired glucose metabolism (Gidlund et al., 2016). Registry entries listing humanin are biomarker studies, not dosing studies ### References - [A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Hashimoto Y, Niikura T, Tajima H, et al., Proceedings of the National Academy of Sciences, 2001](https://doi.org/10.1073/pnas.101133498) - [Humanin peptide suppresses apoptosis by interfering with Bax activation. Guo B, Zhai D, Cabezas E, et al., Nature, 2003](https://doi.org/10.1038/nature01627) - [Humanin: a novel central regulator of peripheral insulin action. Muzumdar RH, Huffman DM, Atzmon G, et al., PLoS One, 2009](https://doi.org/10.1371/journal.pone.0006334) - [Acute humanin therapy attenuates myocardial ischemia and reperfusion injury in mice. Muzumdar RH, Huffman DM, Calvert JW, et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2010](https://doi.org/10.1161/ATVBAHA.110.205997) - [The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Yen K, Mehta HH, Kim SJ, et al., Aging, 2020](https://doi.org/10.18632/aging.103534) - [Circulating humanin is lower in coronary artery disease and is a prognostic biomarker for major cardiac events in humans. Cai H, Cao P, Sun W, et al., Biochimica et Biophysica Acta General Subjects, 2022](https://doi.org/10.1016/j.bbagen.2021.130010) - [Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism. Gidlund EK, von Walden F, Venojarvi M, et al., Physiological Reports, 2016](https://doi.org/10.14814/phy2.13063) - [Humanin induces conformational changes in the apoptosis regulator BAX and sequesters it into fibers, preventing mitochondrial outer-membrane permeabilization. Morris DL, Kastner DW, Johnson S, et al., Journal of Biological Chemistry, 2019](https://doi.org/10.1074/jbc.RA119.011297) ### Side effects No human safety data; effects unknown beyond animal studies, which used intracerebroventricular or intraperitoneal routes that do not translate to subcutaneous dosing. Injection-site irritation is the only commonly reported complaint. Native humanin and the potent analog HNG differ substantially in potency. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not established. No pharmacokinetic study of humanin exists in humans or animals. - Bioavailability: Not measured by any route. Animal studies used intraperitoneal, intravenous or intracerebroventricular administration. - Molecular weight: 2687.14 Da - Sequence: MAPRGFSCLLLLTSEIDLPVKRRA ### Stacks with - [MOTS-c](https://peptidelabs.app/peptides/mots-c/) - [SS-31 (Elamipretide)](https://peptidelabs.app/peptides/ss-31-elamipretide/) - [Epithalon](https://peptidelabs.app/peptides/epithalon/) ### Categories - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## IGF-1 DES URL: https://peptidelabs.app/peptides/igf-1-des/ Also known as: Des(1-3)IGF-1, Des IGF-1, IGF-1 Des Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Truncated IGF-1 missing the N-terminal Gly-Pro-Glu; about 10x as potent as IGF-1 on cultured cells, because losing Glu3 removes most IGF-binding-protein binding. Occurs naturally in colostrum, brain and uterus. Des(1-3)IGF-1 is human IGF-1 without the N-terminal tripeptide Gly-Pro-Glu. It is not purely synthetic: it has been isolated from bovine colostrum, human brain and porcine uterus, and rat serum and tissues convert IGF-1 to it enzymatically (Ballard 1996; Yamamoto and Murphy 1995). Removing Glu3 cuts binding to the IGF-binding proteins, which makes it roughly 10 times more potent than IGF-1 at driving hypertrophy and proliferation in cultured cells; part of that advantage survives in vivo, where the anabolic effect is clearest in gut tissue (Ballard 1996). In pigs and marmosets it was the most potent of the IGFBP-poor variants for lowering plasma glucose (Tomas 1997). No clinical use was ever established and no human trial has been published; proposed clinical uses in catabolic states and inflammatory bowel disease were never evaluated. ### Benefits About 10x the potency of IGF-1 for hypertrophy and proliferation of cultured cells (in vitro); anabolic effects in rats and pigs, most marked in gut tissue; the most potent IGF-1 variant tested for glucose lowering (pig, marmoset). No human data. ### Dosing reference - Research dose: No human data; research-community range 20 to 100 mcg per dose. Animal studies dosed by weight (42 to 270 mcg/kg bolus in marmosets, 20 to 50 mcg/kg in pigs) - Range: 20 to 100 mcg, 1x daily - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 0.1 mg, 1 mg Subcutaneous or intramuscular in research use, often timed around training by community protocols. No half-life has been measured for this peptide, and no published study shows that injecting near a muscle confines the effect to it. Hypoglycemia is the documented dose-limiting effect: in pigs and marmosets des(1-3)IGF-1 was the most potent of the IGF-1 variants tested for lowering plasma glucose (Tomas 1997). ### Mechanism Des(1-3)IGF-1 is the 67-residue form of IGF-1 lacking Gly-Pro-Glu. The missing Glu3 is the residue the IGF-binding proteins need, so the peptide circulates and acts largely unsequestered; its affinity for the type-1 receptor is comparable to or slightly below that of IGF-1, which is why the potency gain is attributed to IGFBP escape rather than receptor binding (Ballard 1996; King 1992). Through IGF-1R it drives PI3K/Akt and mTOR signaling, giving about 10x the effect of IGF-1 on protein synthesis and proliferation in cultured cells. The same loss of IGFBP buffering increases insulin-receptor-mediated glucose lowering in vivo (Tomas 1997). Rat serum and tissues generate des(1-3)IGF-1 from IGF-1, so it is also an endogenous species (Yamamoto and Murphy 1995). ### Evidence Preclinical: animal or in vitro data only - Des(1-3)IGF-1 is about 10x more potent than IGF-1 at stimulating hypertrophy and proliferation of cultured cells, from much reduced IGFBP binding caused by the absence of Glu3; it has been isolated from bovine colostrum, human brain and porcine uterus (Ballard et al., 1996) - Rat serum and tissues convert IGF-1 to des(1-3)IGF-1 enzymatically, making it an endogenous species rather than a purely synthetic analog (Yamamoto and Murphy, 1995) - In marmosets (42 to 270 mcg/kg) and pigs (20 and 50 mcg/kg), des(1-3)IGF-1 was the most potent of five IGF-1 variants for lowering plasma glucose (Tomas et al., 1997) - In pigs, IGF analogs with poor IGFBP affinity produced growth and metabolic effects that differed from IGF-1 and varied with age and GH responsiveness (Walton et al., 1995) - Human-trial status: none. The 1996 review noted clinical opportunities had not been evaluated, and none has been published since ### References - [Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM, International Journal of Biochemistry & Cell Biology, 1996](https://doi.org/10.1016/1357-2725(96)00056-8) - [Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a further potential site of growth hormone regulation of IGF-I action. Yamamoto H, Murphy LJ, Journal of Endocrinology, 1995](https://doi.org/10.1677/joe.0.1460141) - [IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys. Tomas FM, Walton PE, Dunshea FR, Ballard FJ, Journal of Endocrinology, 1997](https://doi.org/10.1677/joe.0.1550377) - [Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. King R, Wells JR, Krieg P, et al., Journal of Molecular Endocrinology, 1992](https://doi.org/10.1677/jme.0.0080029) - [In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. Walton PE, Dunshea FR, Ballard FJ, Progress in Growth Factor Research, 1995](https://doi.org/10.1016/0955-2235(95)00007-0) ### Side effects Hypoglycemia is the documented effect: des(1-3)IGF-1 was the most potent of the IGFBP-poor IGF-1 variants at lowering plasma glucose in pigs and marmosets, with cumulative suppression several times that of IGF-1 (Tomas 1997). No human trial and no human safety data exist. IGF-1R signaling is proliferative, which is why IGF-1 analogs are studied with caution in malignancy. Injection-site swelling and pain are commonly reported (anecdotal). ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured for this peptide; IGFBP-poor IGF-1 variants are cleared from plasma faster than IGF-1 yet suppress glucose for hours (pig, marmoset; Tomas 1997) - Molecular weight: 7365.4 Da - Sequence: TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA (67 aa; mature IGF-1 minus Gly-Pro-Glu) ### Stacks with - [MGF (IGF-1 Ec)](https://peptidelabs.app/peptides/mgf-igf-1-ec/) - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## IGF-1 LR3 URL: https://peptidelabs.app/peptides/igf-1-lr3/ Also known as: Long R3 IGF-1, IGF-1 Long Arginine 3 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview IGF-1 analog with Glu3 replaced by Arg plus a 13-residue N-terminal extension, which binds IGF-binding proteins poorly; in animals it is 2 to 3x as potent as IGF-1 at lowering glucose and is cleared faster, not slower. Long-[Arg3]IGF-I (LR3IGF-I) is a recombinant IGF-1 analog made in E. coli as a fusion protein: Glu3 is replaced by Arg and 13 residues are appended to the N-terminus (Laajoki 2000; King 1992). Both changes cut binding to IGF-binding proteins, and in rat L6 myoblasts the Arg3 substitution alone raised potency for protein and DNA synthesis while slightly lowering type-1 receptor binding, so the gain comes from escaping the binding proteins rather than from better receptor affinity (King 1992). In pigs and marmosets the IGFBP-poor variants were 2 to 3x as potent as IGF-1 at lowering plasma glucose and suppressed glucose for far longer (Tomas 1997). In rats LR3IGF-I was cleared from blood faster than IGF-1 (Shoubridge 2003). It is a laboratory reagent and a veterinary/cell-culture growth factor; no human study exists. ### Benefits 2 to 3x the potency of IGF-1 for glucose lowering (pig, marmoset); increased protein and DNA synthesis in rat L6 myoblasts (in vitro); gut and whole-body growth responses in rats and pigs. No muscle hypertrophy study and no human data. ### Dosing reference - Research dose: No human data; research-community range 20 to 100 mcg daily. Animal studies dosed by weight (20 to 50 mcg/kg in pigs, 2.6 mcg/kg IV in rats) - Range: 20 to 100 mcg, 1x daily - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 0.1 mg, 1 mg Subcutaneous in research use; no human dosing protocol has been published. Site-injection for local growth is not established, and the compound is systemically active. In pigs and marmosets, IGFBP-poor IGF-1 variants lowered plasma glucose 2 to 3x more than IGF-1 and kept it down 4 to 8 times longer by cumulative area, so hypoglycemia is the dose-limiting effect (Tomas 1997). ### Mechanism LR3IGF-I is an 83-residue IGF-1 analog: Glu3 to Arg plus a 13-residue N-terminal extension (MFPAMPLSSLFVN) left over from its methionyl-porcine-GH fusion partner. NMR shows the IGF-1 core is unchanged and only the N-terminal residues are reoriented, which explains the lower affinity for IGF-binding proteins (Laajoki 2000). Because little of the peptide is sequestered by IGFBPs, more is free to activate IGF-1R, and through it PI3K/Akt and mTOR. The analogs bound bovine IGFBP-2 very poorly and the type-1 receptor slightly less well than IGF-1, so reduced IGFBP binding, not receptor affinity, drives the extra potency (King 1992). IGF-1R activation also cross-talks with the insulin receptor, the basis of the hypoglycemia seen in pigs and marmosets (Tomas 1997). ### Evidence Preclinical: animal or in vitro data only - [Arg3]IGF-I and [Gly3]IGF-I were more potent than IGF-1 at stimulating protein and DNA synthesis in rat L6 myoblasts, bound IGFBP-2 very poorly and bound the type-1 receptor slightly less well than IGF-1 (King et al., 1992) - In pigs (20 and 50 mcg/kg) and marmosets (42 to 270 mcg/kg), hypoglycemic potency ran IGF-1 < long-IGF-1 < R3IGF-I = LR3IGF-I < des(1-3)IGF-1, with 2 to 3x the nadir effect and 4 to 8x the cumulative glucose suppression of IGF-1 (Tomas et al., 1997) - Solution NMR of long-[Arg3]IGF-I showed an unchanged IGF-1 fold with a reoriented N-terminus, consistent with its weak IGFBP binding (Laajoki et al., 2000) - After IV bolus in preweaning and adult rats, LR3IGF-I left the circulation faster than IGF-1 and reached gut tissue at a roughly 2:1 ratio (Shoubridge and Read, 2003) - In pigs of different ages, IGF analogs with poor IGFBP affinity produced metabolic and growth effects distinct from IGF-1 (Walton et al., 1995) - Human-trial status: none. No clinical trial of LR3IGF-I has been published or registered; all data are in vitro, rodent, pig and marmoset ### References - [Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. King R, Wells JR, Krieg P, et al., Journal of Molecular Endocrinology, 1992](https://doi.org/10.1677/jme.0.0080029) - [Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. Francis GL, Ross M, Ballard FJ, et al., Journal of Molecular Endocrinology, 1992](https://doi.org/10.1677/jme.0.0080213) - [Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I. Laajoki LG, Francis GL, Wallace JC, et al., Journal of Biological Chemistry, 2000](https://doi.org/10.1074/jbc.275.14.10009) - [IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys. Tomas FM, Walton PE, Dunshea FR, Ballard FJ, Journal of Endocrinology, 1997](https://doi.org/10.1677/joe.0.1550377) - [Preferential intestinal delivery of long[Arg3] insulin-like growth factor (LR3IGF-I) over IGF-I in preweaning and adult rats. Shoubridge CA, Read LC, Endocrinology, 2003](https://doi.org/10.1210/en.2002-220643) - [In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. Walton PE, Dunshea FR, Ballard FJ, Progress in Growth Factor Research, 1995](https://doi.org/10.1016/0955-2235(95)00007-0) ### Side effects Hypoglycemia is the documented risk: in pigs and marmosets, IGFBP-poor IGF-1 variants lowered plasma glucose 2 to 3x more than IGF-1 at the same dose and kept it suppressed several times longer (Tomas 1997). No human trial and no human safety data exist. IGF-1R signaling is proliferative, which is why IGF-1 analogs are studied with caution in malignancy. Injection-site reactions and jaw pain are commonly reported (anecdotal). ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured; cleared from plasma faster than IGF-1 after IV bolus in rats (Shoubridge 2003). The 20 to 30 h figure is community lore and is the wrong direction - Molecular weight: 9111.4 Da - Sequence: MFPAMPLSSLFVN-GP[R]TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA (83 aa; [R] = Arg for Glu3) ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## Ipamorelin URL: https://peptidelabs.app/peptides/ipamorelin/ Also known as: Ipamorelin acetate, NNC 26-0161 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Pentapeptide ghrelin-receptor agonist that released GH without raising ACTH or cortisol in swine (Raun 1998); human data are a PK study (n=40) and one negative phase 2 trial in postoperative ileus (n=114). Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH2, Novo Nordisk NNC 26-0161) was derived from GHRP-1. In rat pituitary cells and anesthetized rats it released GH with potency similar to GHRP-6; in swine it did not raise ACTH or cortisol even at 200 times the GH ED50, unlike GHRP-2 and GHRP-6 (Raun 1998). In rats it increased longitudinal bone growth and body weight (Johansen 1999), bone mineral content (Svensson 2000) and countered glucocorticoid-induced loss of bone formation and muscle strength (Andersen 2001). Human data: a 15-minute IV infusion study in 40 volunteers gave dose-proportional PK, a 2 h half-life and one GH peak at 40 min (Gobburu 1999); a phase 2 randomized trial of 0.03 mg/kg IV twice daily for postoperative ileus found no efficacy difference from placebo (Beck 2014, n=114). No human body-composition trial has been published. ### Benefits GH release without ACTH or cortisol rise (swine), longitudinal bone growth and bone mineral content (rat), counteracted glucocorticoid bone and muscle loss (rat), dose-proportional GH release in human volunteers (PK study) ### Dosing reference - Research dose: Human data: 4-140 nmol/kg IV over 15 min (PK study) and 0.03 mg/kg IV 2x daily (ileus trial); research-community range 100-300 mcg SC 1-3x daily - Range: 100 to 300 mcg, 2-3x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Subcutaneous in research use; human studies used IV infusion. GH peaks about 40 min after IV dosing and returns to baseline within hours (Gobburu 1999). In rats given ipamorelin three times daily for 15 days, the pituitary GH response to a test dose was marginally reduced (Johansen 1999). Rat ileus work used 0.1-1 mg/kg IV four times daily (Venkova 2009). ### Mechanism Ipamorelin is an agonist at the ghrelin receptor GHS-R1a and releases GH through a GHRP-like receptor pathway distinct from GHRH, shown with GHRP and GHRH antagonists in rat pituitary cells (Raun 1998). Its distinguishing property is selectivity: in swine it released GH with potency similar to GHRP-6 but did not raise ACTH, cortisol, FSH, LH, prolactin or TSH (Raun 1998). GH release in humans is dose-dependent, with half-maximal stimulation at a plasma concentration of 214 nmol/L (Gobburu 1999). Like other ghrelin mimetics it accelerates gut transit in rats, the basis of the postoperative-ileus trial (Venkova 2009). ### Evidence Preclinical: animal or in vitro data only - Released GH with GHRP-6-like potency but without ACTH or cortisol rise in swine; no effect on prolactin (Raun et al., 1998) - Dose-proportional PK, 2 h terminal half-life and a single GH peak at 40 min after IV infusion in 40 healthy men (Gobburu et al., 1999) - Increased longitudinal bone growth rate and body weight in rats at 18-450 mcg/day SC (Johansen et al., 1999) - Countered glucocorticoid-induced loss of bone formation and muscle strength in adult rats (Andersen et al., 2001) - Phase 2 RCT in postoperative ileus (0.03 mg/kg IV twice daily, n=114): well tolerated, no efficacy difference from placebo (Beck et al., 2014) - Human-trial status: one PK study and one negative phase 2 RCT; no body-composition trial; not approved anywhere ### References - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) - [Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999](https://doi.org/10.1023/a:1018955126402) - [Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Johansen PB, Nowak J, Skjaerbaek C, et al., Growth Hormone & IGF Research, 1999](https://doi.org/10.1054/ghir.1999.9998) - [The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. Svensson J, Lall S, Dickson SL, et al., Journal of Endocrinology, 2000](https://doi.org/10.1677/joe.0.1650569) - [The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Andersen NB, Malmlof K, Johansen PB, Andreassen TT, Ortoft G, Oxlund H, Growth Hormone & IGF Research, 2001](https://doi.org/10.1054/ghir.2001.0239) - [Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B, Journal of Pharmacology and Experimental Therapeutics, 2009](https://doi.org/10.1124/jpet.108.149211) - [Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014](https://doi.org/10.1007/s00384-014-2030-8) ### Side effects In the ileus RCT, treatment-emergent adverse events were 87.5% with ipamorelin vs 94.8% with placebo in post-surgical patients, with no safety signal (Beck 2014). Injection-site reactions, a transient head rush, mild water retention, and with sustained GH elevation joint aches and reduced insulin sensitivity are commonly reported (anecdotal). Regulatory: ipamorelin acetate is on FDA's 503B category 2 (significant safety risks) table, added 2023-09-29, and in the 503A withdrawn-nomination table, page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~2 h terminal (human, IV infusion; Gobburu 1999) - Molecular weight: 711.86 Da - Sequence: [Aib]H[D-2-Nal][D-F]K[NH2] ### Stacks with - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) - [CJC-1295 no DAC (Mod GRF 1-29)](https://peptidelabs.app/peptides/cjc-1295-no-dac-mod-grf-1-29/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## Kisspeptin-10 URL: https://peptidelabs.app/peptides/kisspeptin-10/ Also known as: Metastin 45-54, Kisspeptin (112-121), KP-10 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Ten-residue C-terminal kisspeptin fragment that activates KISS1R (GPR54); IV doses raised LH and LH pulse frequency in small human studies. Not approved anywhere; on FDA's 503A safety list. Kisspeptins are cleavage products of the KISS1 gene product and are the natural ligands of the receptor GPR54, now KISS1R (Kotani 2001). Kisspeptin-10 is the shortest fully active C-terminal fragment. Human work with it consists of short IV dosing studies in healthy volunteers measuring LH, FSH and testosterone (George 2011; Jayasena 2011; Chan 2011). The IVF egg-maturation and sexual-brain-processing studies often cited for kisspeptin used kisspeptin-54, a different peptide. Listed on FDA's 503A category 2 (safety concerns) page, live table, added 2023-09-29, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Benefits LH and FSH release (human IV physiology studies, men and women), increased LH pulse frequency (healthy men, small studies), IVF egg-maturation trigger (kisspeptin-54 only, not this peptide) ### Dosing reference - Research dose: Community range 100 to 400 mcg subcutaneous; human studies of kisspeptin-10 dosed it intravenously. - Range: 100 to 400 mcg, 1x daily or as directed - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 1 mg, 5 mg Human studies of kisspeptin-10 gave it intravenously; subcutaneous community use is not dose-tested. It stimulates endogenous GnRH release. FDA lists kisspeptin-10 on the live 503A category 2 table (see side effects). ### Mechanism Kisspeptin-10 binds KISS1R (GPR54), a Gq-coupled receptor identified as the kisspeptin receptor in 2001 (Kotani 2001). In humans its effects are consistent with action above the pituitary on GnRH neurons: an IV bolus raised LH within minutes in healthy men, and a continuous infusion increased LH pulse frequency (George 2011). A single bolus also reset the timing of the next GnRH-driven LH pulse (Chan 2011). Responses differ by sex and cycle phase; women in the follicular phase responded much less than men (Jayasena 2011). ### Evidence Preclinical: animal or in vitro data only - IV kisspeptin-10 raised LH in healthy men in a dose-dependent way, and infusion increased LH pulse frequency (George et al., 2011) - LH response to kisspeptin-10 was strong in men and weak in women in the follicular phase (Jayasena et al., 2011) - A single IV bolus of kisspeptin-10 reset the timing of GnRH-driven LH pulses in men (Chan et al., 2011) - Kisspeptin-10 was identified as an active cleavage product binding GPR54 in cell assays (Kotani et al., 2001) - Human-trial status: no kisspeptin-10 trial has tested a clinical outcome; IV kisspeptin-54, a different isoform, stimulated the reproductive axis in men (Dhillo et al., 2005) and triggered egg maturation in IVF (Jayasena et al., 2014); listed on FDA's 503A category 2 page since 2023-09-29 ### References - [The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Kotani M, Detheux M, Vandenbogaerde A, et al., Journal of Biological Chemistry, 2001](https://doi.org/10.1074/jbc.M104847200) - [Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. George JT, Veldhuis JD, Roseweir AK, et al., Journal of Clinical Endocrinology & Metabolism, 2011](https://doi.org/10.1210/jc.2011-0089) - [The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. Jayasena CN, Nijher GM, Comninos AN, et al., Journal of Clinical Endocrinology & Metabolism, 2011](https://doi.org/10.1210/jc.2011-1408) - [Kisspeptin resets the hypothalamic GnRH clock in men. Chan YM, Butler JP, Pinnell NE, et al., Journal of Clinical Endocrinology & Metabolism, 2011](https://doi.org/10.1210/jc.2010-3046) - [Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. Dhillo WS, Chaudhri OB, Patterson M, et al., Journal of Clinical Endocrinology & Metabolism, 2005](https://doi.org/10.1210/jc.2005-1468) - [Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. Jayasena CN, Abbara A, Comninos AN, et al., Journal of Clinical Investigation, 2014](https://doi.org/10.1172/JCI75730) ### Side effects Published human studies are short IV sessions in small groups of healthy volunteers and report hormone changes rather than a systematic safety profile (George 2011; Jayasena 2011). It acutely raises LH, FSH and sex steroids. Repeated-dose effects on the reproductive axis have not been studied in humans. FDA placed kisspeptin-10 on its 503A category 2 list, citing safety concerns for compounding. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No human plasma half-life for kisspeptin-10 confirmed in this pass; ~28 min is the kisspeptin-54 figure from Dhillo 2005, a different isoform, and was removed - Bioavailability: Human studies gave kisspeptin-10 by IV bolus or infusion (George 2011; Chan 2011). No subcutaneous or other non-IV bioavailability figure has been published for this fragment. - Molecular weight: 1302.47 Da - Sequence: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 ### Stacks with - [Gonadorelin (GnRH)](https://peptidelabs.app/peptides/gonadorelin-gnrh/) ### Categories - [Fertility](https://peptidelabs.app/peptides/category/fertility/) - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) - [Sexual Health](https://peptidelabs.app/peptides/category/sexual-health/) ## KPV URL: https://peptidelabs.app/peptides/kpv/ Also known as: alpha-MSH (11-13), ACTH (11-13), Lys-Pro-Val, Tripeptide KPV, 67727-97-3 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview C-terminal tripeptide (Lys-Pro-Val) of alpha-MSH; shown in animal and cell models to suppress NF-kB inflammatory signaling in gut and skin without pigmentation effects. KPV is the C-terminal tripeptide (Lys-Pro-Val) of alpha-MSH, also written alpha-MSH(11-13). Nanomolar concentrations blocked NF-kB and MAP kinase signaling and cut cytokine output in human intestinal epithelial and T cell lines, and oral KPV in drinking water reduced DSS- and TNBS-induced colitis in mice; uptake is via the di/tripeptide transporter PepT1, induced in inflamed colon (Dalmasso 2008). A second group found the same benefit in DSS and transfer colitis, including in mice with a nonfunctional MC1 receptor, so the effect is partly independent of melanocortin receptor signaling (Kannengiesser 2008). It also sped corneal re-epithelialization in rabbits topically (Bonfiglio 2006). No human trial is published, and FDA reports no human exposure data for KPV by any route. ### Benefits NF-kB and MAP kinase inhibition in human intestinal epithelial and T cell lines (in vitro); reduced colitis in mouse DSS, TNBS and transfer models (animal); faster corneal re-epithelialization in rabbits (animal); reduced brain lesion volume after experimental injury in mice (animal). No human data ### Dosing reference - Research dose: 100 to 500 mcg daily: research-community range, no published human dose. Animal work used oral KPV in drinking water, intraperitoneal 1 mg/kg in mice and topical 1 to 10 mg/mL - Range: 100 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Subcutaneous or oral in research use; animal studies used drinking water, intraperitoneal injection and topical application. Oral delivery of the free tripeptide was effective in mice but work since has used nanoparticle or hydrogel carriers to get it past gastric degradation (Xiao 2017). No human pharmacokinetic data exist and no measured half-life is published. ### Mechanism KPV (Lys-Pro-Val) is the C-terminal tripeptide of alpha-MSH. At nanomolar concentrations it inhibited NF-kB and MAP kinase signaling and reduced pro-inflammatory cytokine secretion in human intestinal epithelial lines (Caco2-BBE, HT29-Cl.19A) and Jurkat T cells, acting intracellularly after transport by PepT1; radiolabelled KPV uptake kinetics and competition with a PepT1 substrate established that route (Dalmasso 2008). It works in mice carrying a nonfunctional MC1 receptor, so melanocortin receptor binding is not required and the pigmentation and erectile effects of alpha-MSH analogs do not apply (Kannengiesser 2008). In rabbit cornea the healing effect was blocked by the nitric oxide synthase inhibitor L-NAME, implicating nitric oxide locally (Bonfiglio 2006). ### Evidence Preclinical: animal or in vitro data only - Nanomolar KPV inhibited NF-kB and MAP kinase signaling in human intestinal epithelial and T cell lines via PepT1-mediated uptake, and oral KPV in drinking water reduced DSS- and TNBS-induced colitis in mice (Dalmasso et al., 2008) - KPV reduced inflammatory infiltrate, myeloperoxidase activity and weight loss in DSS and CD45RBhi transfer colitis in mice, and rescued MC1 receptor-deficient mice from death during DSS colitis, so the effect is partly independent of MC1R (Kannengiesser et al., 2008) - Oral KPV prevented colitis-associated tumorigenesis in wild-type mice but had no effect in PepT1-knockout mice, confirming the transporter dependence (Viennois et al., 2016) - KPV loaded into hyaluronic-acid-functionalized nanoparticles and given orally in a hydrogel outperformed free-peptide nanoparticles for mucosal healing and TNF-alpha reduction in mouse colitis, which is the formulation problem the free tripeptide has (Xiao et al., 2017) - Topical KPV at 1 to 10 mg/mL sped corneal re-epithelialization in rabbits, an effect abolished by the nitric oxide synthase inhibitor L-NAME (Bonfiglio et al., 2006) - Human-trial status: none. No trial of KPV is published or registered, and FDA states it has identified no human exposure data for KPV by any route ### References - [PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al., Gastroenterology, 2008](https://doi.org/10.1053/j.gastro.2007.10.026) - [Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Kannengiesser K, Maaser C, Heidemann J, et al., Inflammatory Bowel Diseases, 2008](https://doi.org/10.1002/ibd.20334) - [Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model. Viennois E, Ingersoll SA, Ayyadurai S, et al., Cellular and Molecular Gastroenterology and Hepatology, 2016](https://doi.org/10.1016/j.jcmgh.2016.01.006) - [Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Xiao B, Xu Z, Viennois E, et al., Molecular Therapy, 2017](https://doi.org/10.1016/j.ymthe.2016.11.020) - [Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide. Bonfiglio V, Camillieri G, Avitabile T, Leggio GM, Drago F, Experimental Eye Research, 2006](https://doi.org/10.1016/j.exer.2006.07.014) - [Single administration of tripeptide alpha-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice. Schaible EV, Steinstrasser A, Jahn-Eimermacher A, et al., PLoS One, 2013](https://doi.org/10.1371/journal.pone.0071056) ### Side effects No human study of KPV has been published, and FDA states it has identified no human exposure data for it by any route. In mouse colitis models it reduced inflammation without reported toxicity, and KPV-loaded nanoparticles were nontoxic to intestinal cells in vitro. Lacking the melanocortin core of alpha-MSH, it does not cause the pigmentation or erectile effects of melanotan II, and it worked in MC1 receptor-deficient mice. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in any species; no published pharmacokinetic study - Bioavailability: Oral KPV was active in mouse colitis and is taken up by the PepT1 transporter; no absolute bioavailability has been measured by any route (Dalmasso 2008) - Molecular weight: 342.43 Da - Sequence: Lys-Pro-Val ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [TB-500](https://peptidelabs.app/peptides/tb-500/) - [LL-37](https://peptidelabs.app/peptides/ll-37/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Immune](https://peptidelabs.app/peptides/category/immune/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Larazotide URL: https://peptidelabs.app/peptides/larazotide/ Also known as: AT-1001, INN-202 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic octapeptide (AT-1001) that blocks zonulin-mediated opening of intestinal tight junctions; tested in human celiac disease trials as an adjunct to a gluten-free diet. Larazotide acetate (AT-1001) is an oral eight-residue peptide developed by Alba Therapeutics and later 9 Meters Biopharma as an add-on to a gluten-free diet in celiac disease. Four randomized placebo-controlled trials have been published. In gluten-challenge studies (2.4 to 2.7 g gluten/day) it limited symptom worsening and blunted the rise in anti-transglutaminase IgA, but never separated from placebo on the lactulose/mannitol permeability ratio (Leffler 2012, n=86; Kelly 2013, n=184). A 12-week phase 2b trial in 342 adults already on a gluten-free diet met its symptom endpoint at 0.5 mg three times daily, while 1 and 2 mg did not (Leffler 2015). The phase 3 trial (NCT03569007, n=307) was terminated by the sponsor. Nothing is approved; a 2022 meta-analysis of the four RCTs found symptom benefit only in gluten-challenge subgroups. ### Benefits Reduced gluten-induced symptoms in celiac disease (human RCTs), reduced rise in anti-tTG IgA during gluten challenge (human RCT), tight-junction protection in Caco-2 cells and gliadin-sensitized mice; no effect on measured intestinal permeability in any trial ### Dosing reference - Research dose: 0.25 to 2 mg orally three times daily in trials; only 0.5 mg three times daily met a primary endpoint (n=342) - Range: 250 to 2000 mcg, 3x daily Oral capsule, taken before meals, studied only as an add-on to a continued gluten-free diet. The dose response is inverse: 0.5 mg three times daily beat placebo on symptoms while 1 and 2 mg did not, and in the gluten-challenge study 1 mg worked where 8 mg did not. ### Mechanism Larazotide acetate is an octapeptide (GGVLVQPG) that acts in the gut lumen to keep epithelial tight junctions closed. In Caco-2 and IEC6 monolayers it blocked the ZO-1 and actin redistribution caused by gliadin fragments, by the zonula occludens toxin-derived peptide AT-1002 and by basolateral cytokines, prevented the fall in transepithelial electrical resistance, and reduced translocation of an immunogenic gliadin 13-mer; in gliadin-sensitized HLA-HCD4/DQ8 mice it preserved tight-junction structure and reduced intestinal macrophage accumulation (Gopalakrishnan 2012). It is usually described as a zonulin antagonist, but no binding study to a zonulin receptor has been published, so the receptor-level mechanism is proposed rather than shown. Human trials found no change in the lactulose/mannitol permeability ratio at any dose. ### Evidence Clinical: at least one published human trial or an approved drug - In 86 diet-controlled celiac patients given 2.4 g gluten/day for 14 days, larazotide 0.25 to 8 mg TID did not change the lactulose/mannitol ratio, but lower doses limited the gluten-induced rise in symptom scores (Leffler et al., 2012) - In 184 patients on a 6-week gluten challenge (2.7 g/day), 1 mg TID limited symptoms (p=0.002) and anti-tTG IgA rose 5.8-fold vs 19.0-fold on placebo (p=0.010); the permeability endpoint was again negative (Kelly et al., 2013) - In 342 adults symptomatic despite 12+ months of a gluten-free diet, 0.5 mg TID beat placebo on the celiac GI symptom score over 12 weeks (p=0.022); 1 and 2 mg did not differ from placebo (Leffler et al., 2015) - In Caco-2 cells and gliadin-sensitized transgenic mice it preserved tight-junction structure and blocked gliadin-induced permeability (Gopalakrishnan et al., 2012) - A meta-analysis of the four RCTs (626 patients) found symptom improvement only in the gluten-challenge subgroup and no permeability effect (Hoilat et al., 2022) - Human-trial status: four published phase 2 RCTs; the phase 3 trial (NCT03569007, n=307) was terminated by the sponsor and no regulator has approved it ### References - [A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Leffler DA, Kelly CP, Abdallah HZ, et al., American Journal of Gastroenterology, 2012](https://doi.org/10.1038/ajg.2012.211) - [Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Kelly CP, Green PH, Murray JA, et al., Alimentary Pharmacology & Therapeutics, 2013](https://doi.org/10.1111/apt.12147) - [Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Leffler DA, Kelly CP, Green PH, et al., Gastroenterology, 2015](https://doi.org/10.1053/j.gastro.2015.02.008) - [Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Gopalakrishnan S, Durai M, Kitchens K, et al., Peptides, 2012](https://doi.org/10.1016/j.peptides.2012.02.015) - [Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials. Hoilat GJ, Altowairqi AK, Ayas MF, et al., Clinics and Research in Hepatology and Gastroenterology, 2022](https://doi.org/10.1016/j.clinre.2021.101782) ### Side effects Well tolerated in celiac trials, with headache, nausea, and abdominal discomfort reported at rates near placebo, since it acts locally in the gut with minimal systemic absorption. Urinary tract infection and flatulence were also noted in trials. It is not a substitute for a gluten-free diet. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published human plasma t½; acts in the gut lumen with minimal systemic absorption (oral) - Bioavailability: Oral: Designed for local GI action, minimal systemic absorption - Molecular weight: 725.8 Da - Sequence: GGVLVQPG ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [KPV](https://peptidelabs.app/peptides/kpv/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Immune](https://peptidelabs.app/peptides/category/immune/) ## Liraglutide URL: https://peptidelabs.app/peptides/liraglutide/ Also known as: Victoza, Saxenda, NN2211 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Once-daily acylated GLP-1 analog; FDA-approved for type 2 diabetes (2010) and obesity (2014), with generics since 2024. In SCALE, 3 mg lost 8.4 kg over 56 weeks versus 2.8 kg on placebo. Liraglutide (NN2211) is a GLP-1(7-37) analog from Novo Nordisk with Lys34 replaced by Arg and a palmitic acid on Lys26 through a glutamic acid spacer, which allows albumin binding and once-daily dosing (Knudsen 2000). In SCALE Obesity, 3 mg daily gave 8.4 kg weight loss over 56 weeks versus 2.8 kg with placebo (Pi-Sunyer 2015). In LEADER, it cut major cardiovascular events in type 2 diabetes (Marso 2016). FDA approved Victoza for type 2 diabetes in 2010 and Saxenda for weight in 2014, including adolescents from 12 years. Generic liraglutide has been approved since 2024 and is marketed alongside both brands. ### Benefits Weight loss (human RCT, 3 mg daily), improved glycemic control in type 2 diabetes (approved use), fewer major cardiovascular events in type 2 diabetes (human RCT) ### Dosing reference - Research dose: 0.6-3mg daily - Range: 600 to 3000 mcg, 1x daily - Common vial sizes: 6 mg, 18 mg Subcutaneous, once daily, in the abdomen, thigh or upper arm. Saxenda label titration starts at 0.6 mg daily and rises by 0.6 mg each week to 3 mg; Victoza for type 2 diabetes uses 1.2 to 1.8 mg daily. Approved products are prefilled pens (18 mg/3 mL), not vials. ### Mechanism Liraglutide is a GLP-1 analog with 97% sequence homology to native GLP-1(7-37), made by substituting arginine for lysine at position 34 and attaching palmitic acid through a glutamic acid spacer at Lys26 (Saxenda label). It activates the GLP-1 receptor, raising glucose-dependent insulin secretion, lowering glucagon, delaying gastric emptying and reducing appetite. Self-association and albumin binding slow absorption and protect it from DPP-4 and neutral endopeptidase, extending plasma half-life from 1.5 to 2 minutes for native GLP-1 to about 13 hours (Knudsen 2000; label). ### Evidence Clinical: at least one published human trial or an approved drug - SCALE Obesity (n=3731, 56 weeks): 3 mg daily gave 8.4 kg weight loss versus 2.8 kg with placebo; 63.2% versus 27.1% lost at least 5% (Pi-Sunyer et al., 2015) - LEADER (n=9340, type 2 diabetes, median 3.8 years): major cardiovascular events 13.0% versus 14.9%, hazard ratio 0.87; cardiovascular death hazard ratio 0.78 (Marso et al., 2016) - Healthy men: subcutaneous half-life 12.6 h with dose-proportional exposure (Agersø et al., 2002) - Designed by fatty-acid acylation of GLP-1 for once-daily PK (Knudsen et al., 2000) - Status: FDA-approved and marketed. Victoza (type 2 diabetes, 2010), Saxenda (weight, 2014); generic liraglutide approved from 2024 ### References - [A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. Pi-Sunyer X, Astrup A, Fujioka K, et al., New England Journal of Medicine, 2015](https://doi.org/10.1056/NEJMoa1411892) - [Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. Marso SP, Daniels GH, Brown-Frandsen K, et al., New England Journal of Medicine, 2016](https://doi.org/10.1056/NEJMoa1603827) - [Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. Knudsen LB, Nielsen PF, Huusfeldt PO, et al., Journal of Medicinal Chemistry, 2000](https://doi.org/10.1021/jm9909645) - [The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Agersø H, Jensen LB, Elbrønd B, et al., Diabetologia, 2002](https://doi.org/10.1007/s00125-001-0719-z) - [The Discovery and Development of Liraglutide and Semaglutide. Knudsen LB, Lau J, Frontiers in Endocrinology, 2019](https://doi.org/10.3389/fendo.2019.00155) ### Side effects Nausea, vomiting, diarrhea, and constipation are the most common effects and are generally worst during dose escalation. Pancreatitis, gallbladder disease, and increased heart rate are reported risks, and delayed gastric emptying raises aspiration risk under anesthesia. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months refrigerated - Reconstituted: 30 days at room temp after first use ### Pharmacology - Half-life: ~13 h (subcutaneous, Saxenda label); 12.6 h in healthy men (Agersø 2002) - Bioavailability: Subcutaneous: ~55% - Molecular weight: 3751.2 Da - Sequence: HAEGTFTSDVSSYLEGQAAK[gamma-Glu-palmitoyl]EFIAWLVRGRG ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Livagen URL: https://peptidelabs.app/peptides/livagen/ Also known as: KEDA, Lys-Glu-Asp-Ala, Lyvagen Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide (KEDA) designed from liver peptide preparations; studied mainly in cultured lymphocytes from elderly donors and in rat hepatocytes. Livagen (KEDA, Lys-Glu-Asp-Ala) was made by the St. Petersburg Institute of Bioregulation and Gerontology from the amino acid make-up of liver peptide preparations (Brodskii 2001). In lymphocytes from people over 75 it activated ribosomal genes and decondensed heterochromatin (Khavinson 2002; Lezhava 2007). It raised protein synthesis in rat hepatocytes, most in cells from old rats, inhibited enkephalin-degrading enzymes in human serum (IC50 20 microM; Kost 2003), and given orally to rats moved digestive enzyme activity in old animals toward young values (Timofeeva 2005). A 2020 review from the group reports liver protection in animal hepatitis and fibrosis models (Kuznik 2020). No human trial has been published. ### Benefits Chromatin decondensation in lymphocytes from elderly donors (in vitro), higher protein synthesis in rat hepatocytes (in vitro), enkephalinase inhibition in human serum (in vitro), digestive enzyme changes in old rats (rodent, oral) ### Dosing reference - Research dose: 100 to 200 mcg daily: vendor/community range, no published human dose - Range: 100 to 200 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. Rats received it orally for two weeks; the abstract does not state the dose (Timofeeva 2005). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed, from in vitro work. In lymphocytes from elderly donors it activated ribosomal genes, decondensed pericentromeric heterochromatin and released genes silenced by age-related condensation (Khavinson 2002); it also reduced cobalt-induced chromosome aberrations (Lezhava 2007). It inhibited enkephalin-degrading enzymes in human serum with an IC50 of 20 microM, without binding mu or delta opioid receptors (Kost 2003). In rat hepatocyte cultures it raised protein synthesis and the amplitude of its rhythm (Brodskii 2001). The old claim that it regulates cytochrome P450 genes has no published source. ### Evidence Preclinical: animal or in vitro data only - Activated ribosomal genes and decondensed heterochromatin in cultured lymphocytes from elderly donors (Khavinson et al., 2002) - Reversed age-related heterochromatin condensation and reduced cobalt-induced chromosome aberrations in lymphocytes from people aged 80 to 91 (Lezhava et al., 2007) - Inhibited enkephalin-degrading enzymes in human serum (IC50 20 microM) without binding opioid receptors (Kost et al., 2003) - Raised protein synthesis in rat hepatocyte cultures, most in cells from old animals (Brodskii et al., 2001) - Resisted rat small-intestine peptidases; two weeks of oral dosing moved digestive enzyme activity in old rats toward young values (Timofeeva et al., 2005) - Human-trial status: no published human trial; liver claims rest on animal models summarized in a review by the developer (Kuznik et al., 2020) ### References - [Effects of Livagen peptide on chromatin activation in lymphocytes from old people. Khavinson VKh, Lezhava TA, Monaselidze JG, Dzhokhadze TA, et al., Bulletin of Experimental Biology and Medicine, 2002](https://doi.org/10.1023/a:1021924702103) - [Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. Lezhava T, Jokhadze T, Annals of the New York Academy of Sciences, 2007](https://doi.org/10.1196/annals.1395.043) - [Effect of new peptide bioregulators livagen and epitalon on enkephalin-degrading enzymes in human serum (in Russian). Kost NV, Sokolov OIu, Gabaeva MV, Zolotarev IuA, et al., Izvestiia Akademii Nauk. Seriia Biologicheskaia, 2003](https://pubmed.ncbi.nlm.nih.gov/12942748/) - [Rhythm of protein synthesis in cultures of hepatocytes from rats of different ages. Norm and effect of the peptide livagen (in Russian). Brodskiĭ VIa, Khavinson VKh, Zolotarev IuA, Nechaeva NV, et al., Izvestiia Akademii Nauk. Seriia Biologicheskaia, 2001](https://pubmed.ncbi.nlm.nih.gov/15926314/) - [Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages (in Russian). Timofeeva NM, Khavinson VKh, Malinin VV, Nikitina AA, et al., Advances in Gerontology (Uspekhi Gerontologii), 2005](https://pubmed.ncbi.nlm.nih.gov/16075683/) - [The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology (in Russian). Kuznik BI, Khasanova NB, Ryzhak GA, Mezsheriakova IE, et al., Advances in Gerontology (Uspekhi Gerontologii), 2020](https://pubmed.ncbi.nlm.nih.gov/32362099/) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured. Resists hydrolysis by rat small-intestine peptidases and was active orally in rats (Timofeeva 2005) - Molecular weight: 461.47 Da - Sequence: KEDA (Lys-Glu-Asp-Ala) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Immune](https://peptidelabs.app/peptides/category/immune/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## LL-37 URL: https://peptidelabs.app/peptides/ll-37/ Also known as: Cathelicidin LL-37, hCAP18 (precursor), CAMP (gene), FALL-39 (original name), Ropocamptide (development name) Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview The 37-residue human cathelicidin peptide, an innate-immune effector with broad antimicrobial activity; studied topically in human chronic wound-healing trials and as an immune modulator. LL-37 is the mature 37-residue peptide released from the human cathelicidin precursor hCAP18 in granulocytes (Agerberth et al., 1995; Gudmundsson et al., 1996). It is directly antibacterial in vitro and also acts on host cells, and endogenous hCAP18/LL-37 rises during human skin wound repair while being absent from chronic ulcer epithelium (Heilborn et al., 2003). Clinical development, under the name ropocamptide, has been topical: a 34-patient dose-finding study in venous leg ulcers improved healing at the two lower concentrations (Gronberg et al., 2014), but a 148-patient phase 2b missed its endpoint, with benefit only in a post hoc large-wound subgroup (Mahlapuu et al., 2021). A diabetic foot ulcer trial reported better granulation (Miranda et al., 2023). Elevated endogenous LL-37 drives inflammation in rosacea (Yamasaki et al., 2007). There is no systemic human dosing study. ### Benefits Antimicrobial activity in vitro; faster ulcer healing at low topical concentrations in a 34-patient study but no benefit in the 148-patient phase 2b; better granulation in a diabetic foot ulcer trial ### Dosing reference - Research dose: 50 to 100 mcg daily (community range, no published systemic human dose; trials applied 0.5 to 3.2 mg/mL topically twice weekly) - Range: 50 to 100 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Every published human dose is topical: 0.5, 1.6 or 3.2 mg/mL applied twice weekly for 4 weeks in venous leg ulcers (Gronberg et al., 2014; Mahlapuu et al., 2021) and 0.5 mg/mL cream twice weekly for 4 weeks in diabetic foot ulcers (Miranda et al., 2023). The dose response was inverse in the first study: the lowest concentration performed best and the highest was no better than placebo. An intratumoral study used 250 mcg per tumour weekly (NCT02225366, 4 patients). There is no systemic dosing study and no pharmacokinetic data. Elevated endogenous LL-37 drives rosacea inflammation (Yamasaki et al., 2007) and, complexed with self-DNA, interferon production in psoriasis (Lande et al., 2007). ### Mechanism LL-37 is the only human cathelicidin-derived antimicrobial peptide, cleaved from the hCAP18 precursor in granulocytes (Gudmundsson et al., 1996). It folds into an amphipathic helix that permeabilises microbial membranes. It also acts on host cells: endogenous LL-37 participates in re-epithelialisation of human skin wounds, and blocking it inhibits that repair in organ culture (Heilborn et al., 2003). The same activity drives disease when the peptide is in excess. Increased serine protease activity in rosacea generates cathelicidin fragments that promote skin inflammation (Yamasaki et al., 2007), and LL-37 complexed with self-DNA triggers interferon production by plasmacytoid dendritic cells, the mechanism proposed for psoriasis autoimmunity (Lande et al., 2007). Stability in a non-healing wound environment is limited (PMID 21547341, in sources). ### Evidence Clinical: at least one published human trial or an approved drug - Predicted from a bone marrow cDNA clone as FALL-39 and shown to be antibacterial; the mature granulocyte peptide is LL-37 (Agerberth et al., 1995; Gudmundsson et al., 1996) - hCAP18/LL-37 rises in human skin after wounding, is low in chronic ulcers, and antibodies against it block re-epithelialisation in organ-cultured human skin (Heilborn et al., 2003) - First-in-man trial in 34 patients with hard-to-heal venous leg ulcers: topical LL-37 twice weekly at 0.5 and 1.6 mg/mL raised healing rate constants about six-fold and three-fold versus placebo, while 3.2 mg/mL was no better than placebo (Gronberg et al., 2014) - Phase 2b (HEAL LL-37, n=148) missed its endpoint: no significant healing difference versus placebo in the full population, with a post hoc benefit only in patients whose wounds were at least 10 cm2 (Mahlapuu et al., 2021) - A randomised double-blind trial of LL-37 cream in diabetic foot ulcers (NCT04098562) reported a greater granulation index at days 7 to 28 but no reduction in IL-1 alpha, TNF-alpha or bacterial colonisation (Miranda et al., 2023) - Human-trial status: all controlled human data are topical. Endogenous LL-37 is implicated in rosacea through increased serine protease activity (Yamasaki et al., 2007), and an intratumoral phase 1/2 study in melanoma (NCT02225366) completed with only 4 patients enrolled. No approval anywhere; the development name is ropocamptide ### References - [FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Agerberth B, Gunne H, Odeberg J, et al., Proceedings of the National Academy of Sciences, 1995](https://doi.org/10.1073/pnas.92.1.195) - [The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Gudmundsson GH, Agerberth B, Odeberg J, et al., European Journal of Biochemistry, 1996](https://doi.org/10.1111/j.1432-1033.1996.0325z.x) - [The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. Heilborn JD, Nilsson MF, Kratz G, et al., Journal of Investigative Dermatology, 2003](https://doi.org/10.1046/j.1523-1747.2003.12069.x) - [Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Gronberg A, Mahlapuu M, Stahle M, Whately-Smith C, Rollman O, Wound Repair and Regeneration, 2014](https://doi.org/10.1111/wrr.12211) - [Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Mahlapuu M, Sidorowicz A, Mikosinski J, et al., Wound Repair and Regeneration, 2021](https://doi.org/10.1111/wrr.12977) - [Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial. Miranda E, Bramono K, Yunir E, et al., Archives of Dermatological Research, 2023](https://doi.org/10.1007/s00403-023-02657-8) - [Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Yamasaki K, Di Nardo A, Bardan A, et al., Nature Medicine, 2007](https://doi.org/10.1038/nm1616) - [Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Lande R, Gregorio J, Facchinetti V, et al., Nature, 2007](https://doi.org/10.1038/nature06116) ### Side effects There is no human dosing basis for systemic use; the only human trial was topical. Injection-site inflammation is expected because the peptide is directly pro-inflammatory. Elevated LL-37 is implicated in rosacea, psoriasis, and lupus, so it should be avoided by anyone with inflammatory skin or autoimmune disease. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in humans. The topical trials applied it twice weekly because the peptide is degraded in a non-healing wound environment (Gronberg et al., 2014; stability study in sources). - Bioavailability: Topical application is the only route with human data and acts locally. No systemic bioavailability figure exists; biodistribution has been imaged only in animals by SPECT/CT (PMID 38972467). - Molecular weight: 4493.33 Da - Sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES ### Stacks with - [Thymosin Alpha-1](https://peptidelabs.app/peptides/thymosin-alpha-1/) - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) ### Categories - [Immune](https://peptidelabs.app/peptides/category/immune/) - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## Matrixyl (Palmitoyl Pentapeptide-4) URL: https://peptidelabs.app/peptides/matrixyl-palmitoyl-pentapeptide-4/ Also known as: Palmitoyl Pentapeptide-4, Palmitoyl Pentapeptide-3, Pal-KTTKS, Matrixyl Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Palmitoylated KTTKS, a fragment of the type I procollagen propeptide, applied topically; a 12-week split-face placebo-controlled trial (n=93) at 3 ppm found fewer fine lines and wrinkles. KTTKS (residues 212 to 216 of the type I procollagen C-propeptide) was identified as the minimum sequence that stimulated collagen I, collagen III and fibronectin in fibroblasts (Katayama et al., 1993). The palmitoylated form (Matrixyl, by Sederma) was designed for skin penetration. In a 12-week, double-blind, split-face trial run by Procter & Gamble in 93 women, a moisturizer with 3 ppm pal-KTTKS reduced wrinkles and fine lines versus the same moisturizer alone (Robinson et al., 2005). Larger figures quoted in marketing (for example '68% wrinkle reduction') come from manufacturer data, not peer-reviewed trials. A 2011 review noted few clinical studies and little penetration data (Abu Samah and Heard, 2011). ### Benefits Fine line and wrinkle reduction (human RCT, n=93), collagen I, III and fibronectin stimulation by the KTTKS parent (in vitro) ### Dosing reference - Research dose: Topical, 3 ppm pal-KTTKS in the published single-ingredient RCT; commercial palmitoyl peptides are typically used under 10 ppm. No oral or injectable dose exists. Topical moisturizer or serum. The RCT ran 12 weeks; the multi-ingredient studies applied 0.5 g twice daily for 4 weeks. Trade solutions are far more dilute than the active peptide, so labels quoting a few percent of Matrixyl correspond to a few ppm of peptide. ### Mechanism Proposed matrikine signalling. The unmodified KTTKS fragment stimulated collagen I, collagen III and fibronectin production in fibroblasts and other mesenchymal cells without changing total protein synthesis (Katayama et al., 1993). The palmitoyl chain improves stability and skin entry: in hairless mouse skin pal-KTTKS reached the stratum corneum, epidermis and dermis, while KTTKS was not detected in any layer (Choi et al., 2014). Collagen IV induction, TGF-beta activation and a 'wound-repair' signal are not shown in primary sources for this compound. ### Evidence Clinical: at least one published human trial or an approved drug - KTTKS was the minimal procollagen fragment that stimulated collagen I, III and fibronectin in fibroblasts (Katayama et al., 1993) - 12-week double-blind split-face RCT, 93 women aged 35 to 55: 3 ppm pal-KTTKS reduced wrinkles and fine lines vs placebo moisturizer by image analysis (Robinson et al., 2005) - Two split-face RCTs (n=42 and n=35) of multi-ingredient products containing pal-KTTKS improved periorbital roughness in 4 weeks; the peptide's share is not separable (Kaczvinsky et al., 2009) - Pal-KTTKS, unlike KTTKS, reached epidermis and dermis in hairless mouse skin in vitro (Choi et al., 2014) - Human-trial status: one single-ingredient RCT, run by a commercial user (Procter & Gamble); other human data are multi-ingredient or manufacturer figures ### References - [A pentapeptide from type I procollagen promotes extracellular matrix production. Katayama K, Armendariz-Borunda J, Raghow R, Kang AH, et al., The Journal of biological chemistry, 1993](https://pubmed.ncbi.nlm.nih.gov/8486721/) - [Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, et al., International journal of cosmetic science, 2005](https://doi.org/10.1111/j.1467-2494.2005.00261.x) - [Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS). Choi YL, Park EJ, Kim E, Na DH, et al., Biomolecules & therapeutics, 2014](https://doi.org/10.4062/biomolther.2014.053) - [Topically applied KTTKS: a review. Abu Samah NH, Heard CM, International journal of cosmetic science, 2011](https://doi.org/10.1111/j.1468-2494.2011.00657.x) - [Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging. Kaczvinsky JR, Griffiths CE, Schnicker MS, Li J, Journal of cosmetic dermatology, 2009](https://doi.org/10.1111/j.1473-2165.2009.00444.x) - [Topical Peptide Treatments with Effective Anti-Aging Results. Schagen S, Cosmetics, 2017](https://doi.org/10.3390/cosmetics4020016) ### Side effects Well tolerated in the 93-person 12-week RCT (Robinson et al., 2005). No other safety study of pal-KTTKS has been published. Commonly reported (anecdotal): mild irritation or redness. Labels quoting trade-solution percentages and papers quoting ppm of active peptide differ by roughly a hundredfold. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data; pal-KTTKS was degraded in hairless mouse skin extracts, more slowly than KTTKS - Bioavailability: Topical (hairless mouse skin in vitro): 4.2, 2.8 and 0.3 ug/cm2 in stratum corneum, epidermis and dermis; none crossed full-thickness skin - Molecular weight: 802.05 Da - Sequence: Palmitoyl-Lys-Thr-Thr-Lys-Ser (pal-KTTKS) ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Mazdutide URL: https://peptidelabs.app/peptides/mazdutide/ Also known as: IBI362, LY3305677, Xinermei Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Oxyntomodulin-based GLP-1 and glucagon receptor dual agonist peptide; approved in China by the NMPA in 2025 for weight management and type 2 diabetes; 14.0% weight loss at 6 mg over 48 weeks in phase 3. Mazdutide (IBI362, LY3305677) is a 33-residue synthetic analog of mammalian oxyntomodulin carrying a C20 fatty diacid for once-weekly subcutaneous dosing, developed by Eli Lilly with Innovent Biologics. It activates GLP-1 and glucagon receptors and does not target GIP receptors; the triple agonist in the catalog is retatrutide. In phase 3 GLORY-1 (n=610, China), weight fell 11.0% at 4 mg and 14.0% at 6 mg over 48 weeks vs a 0.3% gain on placebo (Ji 2025); 9 mg gave 16.7% at 60 weeks in GLORY-2 (Gao 2026). A US phase 2 by Lilly tested up to 16 mg (Hsia 2026). China's NMPA approved it as Xinermei in June 2025 for long-term weight management and in September 2025 for type 2 diabetes (Shirley 2025). No approval is listed in Drugs@FDA. ### Benefits Weight loss (human phase 3 RCTs), lower HbA1c in type 2 diabetes (human phase 3 RCT), improved cardiometabolic measures (human phase 3 RCT) ### Dosing reference - Research dose: 3 to 9 mg once weekly: phase 3 maintenance doses 4, 6 and 9 mg (GLORY-1, GLORY-2, DREAMS-1); phase 2 tested 3 to 6 mg in China and 3 to 16 mg in the US - Range: 3000 to 9000 mcg, 1x weekly - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 6 mg, 12 mg Subcutaneous, once weekly. Phase 1b escalated in 4-week steps (2, 4, then 6 mg) over 12 weeks (Ji 2021). GLORY-1 treated for 48 weeks at 4 or 6 mg; GLORY-2 for 60 weeks at 9 mg. The US phase 2 held 3 mg to week 32 before stepping to 6 mg, and also tested 10 and 16 mg (Hsia 2026). ### Mechanism Mazdutide is a long-acting oxyntomodulin analog that binds and activates both the GLP-1 receptor and the glucagon receptor; it has no GIP receptor activity. Preclinical work summarised by Ji 2021 found it lowered body weight in both glucagon-receptor and GLP-1-receptor knockout mice, so each receptor contributes. A C20 diacid joined through gamma-Glu and two OEG spacers to Lys20 binds albumin and gives a terminal half-life of about 6 to 17 days (Ji 2021; PubChem). GLP-1 receptor activity is linked to reduced appetite and glucose-dependent insulin secretion; glucagon receptor activity is proposed to add hepatic fat oxidation and energy expenditure. Heart rate rose with dose, most at 6 mg, in phase 1b (Ji 2021). ### Evidence Clinical: at least one published human trial or an approved drug - Phase 1b, 12 weeks (n=36, China): weight change -4.8% to -6.4% vs +0.6% with placebo; half-life 151 to 404 h (Ji et al., 2021) - Phase 2, 24 weeks (n=248, China): -6.7% (3 mg), -10.4% (4.5 mg), -11.3% (6 mg) vs +1.0% with placebo (Ji et al., 2023) - Phase 3 GLORY-1, 48 weeks (n=610, China): -11.0% (4 mg) and -14.0% (6 mg) vs +0.3% with placebo; adverse-event discontinuation 0.5 to 1.5% (Ji et al., 2025) - Phase 3 GLORY-2, 9 mg, 60 weeks (n=461, BMI 30 or higher): -16.7% vs -1.5% with placebo; vomiting 53.1%, nausea 46.9% (Gao et al., 2026) - Phase 3 DREAMS-1, type 2 diabetes, 24 weeks (n=320): HbA1c -1.57 (4 mg) and -2.15 points (6 mg) vs -0.14 with placebo (Zhu et al., 2026) - Human-trial status: approved in China (NMPA) June 2025 for weight management and September 2025 for type 2 diabetes (Shirley, 2025); no FDA approval; US phase 2 up to 16 mg completed (Hsia et al., 2026) ### References - [IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. Ji L, Jiang H, An P, et al., EClinicalMedicine, 2021](https://doi.org/10.1016/j.eclinm.2021.101088) - [A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Ji L, Jiang H, Cheng Z, et al., Nature Communications, 2023](https://doi.org/10.1038/s41467-023-44067-4) - [Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. Ji L, Jiang H, Bi Y, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2411528) - [Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. Gao L, Jiang H, Cai H, et al., JAMA, 2026](https://doi.org/10.1001/jama.2026.8142) - [Mazdutide versus placebo in Chinese adults with type 2 diabetes. Zhu D, Zhao J, Cai H, et al., Nature, 2026](https://doi.org/10.1038/s41586-025-10026-w) - [Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial. Hsia SH, Bays HE, Billings LK, et al., The Lancet Diabetes & Endocrinology, 2026](https://doi.org/10.1016/S2213-8587(26)00160-9) - [Mazdutide: First Approval. Shirley M, Drugs, 2025](https://doi.org/10.1007/s40265-025-02249-y) ### Side effects Gastrointestinal events dominate. At 9 mg in GLORY-2, vomiting 53.1%, nausea 46.9% and diarrhoea 39.4% vs 1.3%, 3.2% and 6.5% on placebo, mostly mild to moderate; 2.9% stopped (Gao 2026). At 4 to 6 mg, diarrhoea, nausea and decreased appetite were most common (Zhu 2026; Ji 2023). In phase 1b, heart rate rose most at 6 mg and three participants had mild asymptomatic ECG findings (Ji 2021). In the US phase 2, 20% stopped for adverse events at 16 mg (Hsia 2026). GLP-1 class warnings (pancreatitis, gallbladder disease, rodent thyroid C-cell tumours) appear on approved GLP-1 agonist labels; long-term mazdutide data are limited. ### Storage - Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 24+ months refrigerated - Reconstituted: 28 days refrigerated (general lyophilised-peptide guidance) ### Pharmacology - Half-life: 151 to 404 h, individual range (adults with overweight or obesity, subcutaneous); median tmax 72 h (Ji 2021) - Bioavailability: No absolute bioavailability published; slow subcutaneous absorption, Cmax at 12 to 120 h (human, Ji 2021) - Molecular weight: 4476.1 Da - Sequence: H[Aib]QGTFTSDYSKYLDEKKAK[C20 diacid-gamma-Glu-OEG-OEG on Lys20]EFVEWLLEGGPSG-NH2 ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Melanostatin DM URL: https://peptidelabs.app/peptides/melanostatin-dm/ Also known as: H-His-D-Arg-Ala-Trp-D-Phe-Lys-NH2, HrAWfK-NH2 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic hexapeptide (His-D-Arg-Ala-Trp-D-Phe-Lys-NH2), an MSH and GHRP hybrid that blocked alpha-MSH skin darkening in frogs and lizards; it was inactive in mouse melanoma cells. The name suggests the hypothalamic peptide melanostatin (MIF-1, Pro-Leu-Gly-NH2), but this product is a different molecule: a hexapeptide hybrid of a growth hormone-releasing peptide analog and alpha-MSH(6-11) from Sawyer, Castrucci and Hadley (Sawyer et al., 1989). Injected into lizards it halved or abolished alpha-MSH skin darkening (Castrucci et al., 1994). It also blocked alpha-MSH in frog and anole skin, but had no agonist or antagonist activity in mouse melanoma cells or in a fish species (Castrucci et al., 1997), so effects on mammalian pigment cells are unproven. No topical study in any species and no human study has been published. ### Benefits Blocks alpha-MSH skin darkening (lizard in vivo, frog and lizard skin in vitro); no mammalian or human data ### Dosing reference - Research dose: Topical by vendor framing only; no study in any species has applied it to skin, and no published formulation concentration exists. Lizard studies injected 1 to 10 nmol per 5 g body weight. Sold as a topical peptide. All published work used injection in lizards or isolated frog and lizard skin; no topical concentration has been studied. ### Mechanism Proposed competitive alpha-MSH antagonism at the MC1-type receptor of amphibian and reptile melanophores. MSH and GHRP hybrids with a D-Arg-Ala pair inhibited alpha-MSH on frog and anole skin with pA2 of about 5 to 6 (Sawyer et al., 1989), and the compound blocked alpha-MSH darkening in live lizards (Castrucci et al., 1994). It was inactive in murine melanoma cells, which the authors attribute to species differences in MC1 receptors (Castrucci et al., 1997). Effects on human MC1R, cAMP or tyrosinase have not been tested. ### Evidence Preclinical: animal or in vitro data only - MSH and GHRP hybrid analogs with D-Arg-Ala substitutions inhibited alpha-MSH on frog and anole lizard skin in vitro (Sawyer et al., 1989) - Injected into white-adapted lizards, 1 nmol per 5 g abolished alpha-MSH darkening in U. ornatus and 10 nmol halved it in S. jarrovii (Castrucci et al., 1994) - Antagonist in Anolis lizard skin but inactive in a teleost fish and in murine melanoma cells (Castrucci et al., 1997) - Human-trial status: no human, topical or mammalian in vivo study; all data are from one group's amphibian and reptile assays ### References - [Discovery and structure-activity relationships of novel alpha-melanocyte-stimulating hormone inhibitors. Sawyer TK, Staples DJ, Castrucci AM, Hadley ME, Peptide research, 1989](https://pubmed.ncbi.nlm.nih.gov/2562482/) - [Discovery of an alpha-melanotropin antagonist effective in vivo. Castrucci AM, Sherbrooke WC, Sawyer TK, Staples DJ, et al., Peptides, 1994](https://doi.org/10.1016/0196-9781(94)90086-8) - [Comparative biological activities of alpha-MSH antagonists in vertebrate pigment cells. Castrucci AM, Almeida AL, al-Obeidi FA, Hadley ME, et al., General and comparative endocrinology, 1997](https://doi.org/10.1006/gcen.1996.6844) ### Side effects No safety data in any species. The design is based on a growth hormone-releasing peptide analog, and whether it keeps any GH-releasing activity has not been reported. Commonly reported (anecdotal): none documented. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured; skin penetration has never been studied - Molecular weight: 843.01 Da - Sequence: His-[D-Arg]-Ala-Trp-[D-Phe]-Lys-NH2 ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Melanotan 1 URL: https://peptidelabs.app/peptides/melanotan-1/ Also known as: Afamelanotide, Scenesse, CUV1647, NDP-α-MSH, Melanotan I, MT-I, [Nle4,D-Phe7]-alpha-MSH Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic alpha-MSH analog (afamelanotide, [Nle4,D-Phe7]-alpha-MSH) and MC1R agonist; a 16 mg implant is approved in the EU (2014) and US (2019) for erythropoietic protoporphyria. Melanotan 1 is the research name for afamelanotide, made at the University of Arizona in 1980 as an enzyme-resistant, longer-acting alpha-MSH analog. Daily subcutaneous injections darkened skin in healthy men in a 1991 randomized trial. A 16 mg controlled-release implant (SCENESSE) was authorised by EMA in December 2014 under exceptional circumstances and approved by FDA in October 2019 (NDA 210797) to increase pain-free light exposure in adults with erythropoietic protoporphyria; it is still marketed in both regions. A phase 3 vitiligo trial with NB-UVB is active. The lyophilized powder sold as 'Melanotan 1' for self-injection is not the approved implant and has no approval or quality standard of its own. ### Benefits Skin darkening without UV (human RCT, SC injection), more pain-free light exposure in erythropoietic protoporphyria (approved implant, phase 3 RCTs), faster vitiligo repigmentation with NB-UVB (1 RCT, implant) ### Dosing reference - Research dose: 500 to 1000 mcg daily loading: community range for the unlicensed powder. Approved product is a 16 mg implant every 2 months; early SC trials used 0.08 to 0.21 mg/kg daily - Range: 500 to 1000 mcg, 1x daily (loading) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Approved use: one 16 mg SCENESSE implant inserted subcutaneously by a trained professional every 2 months (FDA label). Early saline-injection trials gave 0.08 to 0.21 mg/kg SC daily on weekdays for 2 weeks (10 doses), 10x or more above the community 0.5 to 1 mg loading range, which has no published protocol. Oral dosing produced no measurable plasma levels. ### Mechanism Afamelanotide is labeled as a melanocortin 1 receptor (MC1R) agonist. MC1R activation on melanocytes increases eumelanin synthesis, the proposed basis of reduced phototoxicity in erythropoietic protoporphyria. The Nle4 and D-Phe7 substitutions make it resistant to serum enzymes, with prolonged activity and about 26 times the potency of alpha-MSH in a melanoma adenylate cyclase assay (Sawyer et al., 1980). MC1R signaling is also reported to induce antioxidant activity and DNA repair and to modulate inflammation (Minder et al., 2017). Its activity at MC3R and MC4R is not characterized in the cited sources. ### Evidence Clinical: at least one published human trial or an approved drug - Randomized double-blind trial in 28 healthy men: 10 SC injections over 12 days darkened skin in both poor and good tanners, with no change on saline; peak 1 to 3 weeks after dosing (Levine et al., 1991) - SC doses of 0.08 to 0.21 mg/kg were fully bioavailable relative to IV, oral dosing gave no detectable plasma levels, and the beta half-life was 0.8 to 1.7 h (Ugwu et al., 1997) - Two phase 3 RCTs of a 16 mg implant every 60 days in erythropoietic protoporphyria (EU n=74, US n=94) increased pain-free direct sunlight time (US median 69.4 vs 40.8 h; EU 6.0 vs 0.8 h) (Langendonk et al., 2015) - Implant plus NB-UVB gave faster and greater repigmentation than NB-UVB alone in nonsegmental vitiligo (48.6% vs 33.3% at day 168; n=55) (Lim et al., 2015) - Observational study of 115 EPP patients over up to 8 years: quality of life rose from 31% to 74% of maximum, with mainly nausea as the attributable adverse event (Biolcati et al., 2015) - Regulatory and trial status: SCENESSE 16 mg implant authorised by EMA 22 Dec 2014 and approved by FDA 8 Oct 2019 (NDA 210797) for adults with EPP, still marketed; phase 3 vitiligo trial NCT06109649 active. Approvals cover the implant, not the injectable powder sold as Melanotan 1 ### References - [Afamelanotide for Erythropoietic Protoporphyria. Langendonk JG, Balwani M, Anderson KE, et al., The New England Journal of Medicine, 2015](https://doi.org/10.1056/NEJMoa1411481) - [Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin. Levine N, Sheftel SN, Eytan T, et al., JAMA, 1991](https://doi.org/10.1001/jama.1991.03470190078033) - [Skin pigmentation and pharmacokinetics of melanotan-I in humans. Ugwu SO, Blanchard J, Dorr RT, et al., Biopharmaceutics & Drug Disposition, 1997](https://doi.org/10.1002/(sici)1099-081x(199704)18:3<259::aid-bdd20>3.0.co;2-x) - [Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. Lim HW, Grimes PE, Agbai O, et al., JAMA Dermatology, 2015](https://doi.org/10.1001/jamadermatol.2014.1875) - [Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Biolcati G, Marchesini E, Sorge F, et al., The British Journal of Dermatology, 2015](https://doi.org/10.1111/bjd.13598) - [Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Minder EI, Barman-Aksoezen J, Schneider-Yin X, Clinical Pharmacokinetics, 2017](https://doi.org/10.1007/s40262-016-0501-5) - [4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Sawyer TK, Sanfilippo PJ, Hruby VJ, et al., Proceedings of the National Academy of Sciences of the United States of America, 1980](https://doi.org/10.1073/pnas.77.10.5754) ### Side effects EPP trials of the implant through month 6 (n=125 vs 119 vehicle): implant-site reaction 21% vs 10%, nausea 19% vs 14%, oropharyngeal pain 7% vs 5%, cough, fatigue, skin hyperpigmentation 4% vs 0%, melanocytic nevus 4% vs 2% (FDA label). The label warns of darkening of pre-existing nevi and freckles, calls for twice-yearly full-body skin exams, and lists serious hypersensitivity including anaphylaxis. Saline-injection studies reported occasional GI upset and facial flushing (Ugwu et al., 1997). No quality data exist for the unlicensed powder. Commonly reported (anecdotal): nausea, flushing, darkening of moles. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Implant: apparent ~15 h, median Tmax 36 h (human, label). SC injection in saline: beta phase 0.8 to 1.7 h (human, n=3) - Bioavailability: SC injection: complete relative to IV (human, n=3). Oral: no detectable plasma levels (human). Implant: controlled release, one implant every 2 months - Molecular weight: 1646.88 Da - Sequence: [Ac-S]YS[Nle]EH[D-F]RWGKPV[NH2] ### Categories - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) ## Melanotan II URL: https://peptidelabs.app/peptides/melanotan-ii/ Also known as: MT-II, MT2, Melanotan 2 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic cyclic alpha-MSH(4-10) analog that binds MC1, MC3, MC4 and MC5 receptors; small 1990s human trials found skin darkening and erections. Never approved. Melanotan II (MT-II) was made at the University of Arizona as a lactam-bridged, enzyme-resistant fragment of alpha-MSH. A 1996 pilot in 3 healthy men produced tanning plus spontaneous erections, nausea and yawning, which led to two small placebo-controlled crossover trials in erectile dysfunction (n=10 each). Development moved to the close derivative bremelanotide (PT-141, a separate catalog entry), and MT-II was never approved anywhere. Product sold online for tanning is unlicensed, and case reports describe melanoma, rhabdomyolysis, priapism and renal infarction after use. Listed on FDA's 503A category 2 (safety concerns) page, withdrawn-nomination table, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ### Benefits Skin tanning (pilot human study, n=3), erections in men with erectile dysfunction (2 crossover RCTs, n=10 each), increased sexual desire (1 RCT, n=10), reduced food intake (mouse, central dosing) ### Dosing reference - Research dose: 250 to 500 mcg daily loading: community range, no published protocol. Human trials used 0.01 to 0.03 mg/kg SC (weight-based) - Range: 250 to 500 mcg, 1x daily (loading) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Human trials used weight-based subcutaneous doses: 0.01 to 0.03 mg/kg on alternate weekdays for 2 weeks in the pilot (0.025 mg/kg was recommended for further study), and single 0.025 mg/kg doses in the erectile dysfunction trials. The loading then 1 to 2x weekly maintenance pattern is community practice with no published protocol. Nausea, yawning, flushing and spontaneous erections were common after first doses in the trials. ### Mechanism Cyclic lactam analog of alpha-MSH(4-10) with Nle4 and D-Phe7 substitutions. Binding studies on cells expressing human receptors show high affinity at MC1, MC3, MC4 and MC5 receptors. MC1R activation on melanocytes is the proposed route to more eumelanin, consistent with the tanning seen in humans (Dorr et al., 1996). Central MC3/MC4 agonism suppresses feeding: intracerebroventricular MT-II inhibited food intake in four mouse models of hyperphagia, and the antagonist SHU9119 blocked the effect (Fan et al., 1997). In rats, MT-II induced erections through brain and spinal melanocortin receptors, the proposed basis of the erections in the human trials. ### Evidence Clinical: at least one published human trial or an approved drug - Pilot phase 1 in 3 healthy men: SC 0.01 to 0.03 mg/kg on alternate weekdays for 2 weeks increased facial and upper-body pigmentation; nausea, yawning and spontaneous erections were common (Dorr et al., 1996) - Double-blind crossover in 10 men with psychogenic erectile dysfunction: 0.025 mg/kg SC produced erections in 8 of 10, with tip rigidity over 80% lasting 38.0 vs 3.0 min on placebo (Wessells et al., 1998) - Crossover in 10 men with organic erectile dysfunction: erections after 12 of 19 MT-II injections vs 1 of 21 placebo, higher sexual desire, severe nausea after 4 of 19 injections (Wessells et al., 2000) - Intracerebroventricular MT-II inhibited feeding in four mouse models of hyperphagia, blocked by the antagonist SHU9119 (Fan et al., 1997) - Case reports after unlicensed use: melanoma (Hjuler and Lorentzen, 2014), sympathomimetic toxicity with rhabdomyolysis (Nelson et al., 2012), ischemic priapism (Mallory et al., 2021), renal infarction (Peters et al., 2020) - Human-trial status: never approved, and no trial since the small 1990s studies has published results. The derivative bremelanotide was approved by FDA in 2019 (Vyleesi, NDA 210557). Registered vitiligo record NCT07437560 calls itself an example record and is not evidence ### References - [Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Dorr RT, Lines R, Levine N, et al., Life Sciences, 1996](https://doi.org/10.1016/0024-3205(96)00160-9) - [Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. Wessells H, Fuciarelli K, Hansen J, et al., The Journal of Urology, 1998](https://doi.org/10.1097/00005392-199808000-00025) - [Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Wessells H, Gralnek D, Dorr R, et al., Urology, 2000](https://doi.org/10.1016/s0090-4295(00)00680-4) - [Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Fan W, Boston BA, Kesterson RA, et al., Nature, 1997](https://doi.org/10.1038/385165a0) - [Melanoma associated with the use of melanotan-II. Hjuler KF, Lorentzen HF, Dermatology, 2014](https://doi.org/10.1159/000356389) - [Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Nelson ME, Bryant SM, Aks SE, Clinical Toxicology, 2012](https://doi.org/10.3109/15563650.2012.740637) - [Melanotan Tanning Injection: A Rare Cause of Priapism. Mallory CW, Lopategui DM, Cordon BH, Sexual Medicine, 2021](https://doi.org/10.1016/j.esxm.2020.100298) - [Melanotan II: a possible cause of renal infarction: review of the literature and case report. Peters B, Hadimeri H, Wahlberg R, et al., CEN Case Reports, 2020](https://doi.org/10.1007/s13730-020-00447-z) ### Side effects In the 1990s trials (n=3 and two of n=10), nausea, stretching and yawning, reduced appetite and spontaneous erections were common; 0.03 mg/kg caused grade II somnolence and fatigue in one subject, and 4 of 19 injections caused severe nausea (Wessells et al., 2000). Case reports after unlicensed use: melanoma in a 20-year-old after a 3 to 4 week course with sunbed use (Hjuler and Lorentzen, 2014); sympathomimetic toxicity, rhabdomyolysis (CK 17,773 IU/L) and renal dysfunction after a 6 mg injection (Nelson et al., 2012); acute ischemic priapism needing surgical decompression (Mallory et al., 2021); renal infarction (Peters et al., 2020); posterior reversible encephalopathy syndrome. FDA's category 2 entry cites possible immunogenicity and these case reports. Commonly reported (anecdotal): facial flushing, darkening of existing moles and new moles. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No published human value. Rat IV (0.3 mg/kg): biphasic disposition; the beta half-life differed between HPLC and bioassay methods - Bioavailability: Subcutaneous: not measured in humans. Oral: 4.6% reported in rats in a 1994 preformulation study - Molecular weight: 1024.18 Da - Sequence: [Ac-Nle]DH[D-F]RWK[NH2] [lactam bridge between Asp and Lys side chains] ### Categories - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Sexual Health](https://peptidelabs.app/peptides/category/sexual-health/) - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) ## Methylene Blue URL: https://peptidelabs.app/peptides/methylene-blue/ Also known as: Methylthioninium chloride, MB, ProvayBlue Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Phenothiazine redox dye (not a peptide) that can act as an alternative electron carrier in mitochondria; low oral doses studied in humans for memory and cerebral metabolism. Methylene blue is a phenothiazine dye, not a peptide. In the US it is an approved prescription drug, ProvayBlue (NDA 204630, approved 2016-04-08), given intravenously for acquired methemoglobinemia, with a boxed warning for serotonin syndrome. At low oral doses it has been studied in small human trials of memory and fear extinction with mixed results. A related reduced form, LMTM, failed a phase 3 trial in Alzheimer's disease. The cognitive uses are research uses, not approved indications. ### Benefits Acquired methemoglobinemia (approved IV drug, ProvayBlue), memory and fear-extinction effects (small human RCTs, mixed), mitochondrial electron carrier (preclinical) ### Dosing reference - Research dose: 0.5-20 mg daily (oral, low dose) - Range: 500 to 20000 mcg, 1x daily 0.5-20mg oral, start low. Pharmaceutical/USP grade only - industrial or aquarium dye contains heavy-metal contaminants. DO NOT combine with SSRIs, SNRIs, MAOIs, triptans or other serotonergic drugs: methylene blue is a potent MAO-A inhibitor and has caused serotonin syndrome at clinical doses. Avoid in G6PD deficiency (hemolysis) and in pregnancy. Effects are hormetic - high doses become pro-oxidant. Temporarily stains urine blue. ### Mechanism Methylene blue is a redox-active phenothiazine. In methemoglobinemia it is reduced to leucomethylene blue, which converts methemoglobin back to hemoglobin. In mitochondria it can accept electrons from NADH and pass them to cytochrome c, bypassing complex I to III blockade, and at low doses it increased mitochondrial respiration in preclinical work. It also inhibits monoamine oxidase A, the basis of the serotonin syndrome warning on the US label, and nitric oxide synthase. ### Evidence Clinical: at least one published human trial or an approved drug - Approved in the US in 2016 as ProvayBlue (NDA 204630) for acquired methemoglobinemia, IV, with a boxed warning for serotonin syndrome with serotonergic drugs; still marketed - An aqueous oral formulation had 72.3% absolute bioavailability in healthy volunteers (Walter-Sack et al., 2009) - A randomized placebo-controlled fMRI study gave healthy adults a single low oral dose and measured memory and brain activation (Rodriguez et al., 2016) - In adults with claustrophobia, post-session methylene blue improved fear extinction when the exposure session ended with low fear and worsened it when fear stayed high (Telch et al., 2014) - Low-dose methylene blue improved extinction memory in rats (Gonzalez-Lima and Bruchey, 2004) - Human-trial status beyond the approved use: small trials only. LMTM, a reduced methylthioninium form, failed its phase 3 trial in mild to moderate Alzheimer's disease (Gauthier et al., 2016) ### References - [Extinction Memory Improvement by the Metabolic Enhancer Methylene Blue. Gonzalez-Lima F, Bruchey AK, Learning & Memory, 2004](https://doi.org/10.1101/lm.82404) - [High absolute bioavailability of methylene blue given as an aqueous oral formulation. Walter-Sack I, Rengelshausen J, Oberwittler H, et al., European Journal of Clinical Pharmacology, 2009](https://doi.org/10.1007/s00228-008-0563-x) - [Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. Rodriguez P, Zhou W, Barrett DW, et al., Radiology, 2016](https://doi.org/10.1148/radiol.2016152893) - [Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia. Telch MJ, Bruchey AK, Rosenfield D, et al., American Journal of Psychiatry, 2014](https://doi.org/10.1176/appi.ajp.2014.13101407) - [Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Gauthier S, Feldman HH, Schneider LS, et al., The Lancet, 2016](https://doi.org/10.1016/S0140-6736(16)31275-2) ### Side effects The US label carries a boxed warning: methylene blue inhibits MAO-A and can cause serotonin syndrome with SSRIs, SNRIs, MAOIs, triptans and other serotonergic drugs, a documented cause of hospitalization and death. It causes hemolysis in G6PD deficiency and turns urine and stool blue-green. High doses can paradoxically cause methemoglobinemia. ### Storage - Storage: Room temperature, away from light - Lyophilized: 24+ months ### Pharmacology - Half-life: About 24 h (human, IV; ProvayBlue label) - Bioavailability: Oral: 72.3% absolute (healthy volunteers, aqueous solution vs IV; Walter-Sack et al., 2009) - Molecular weight: 319.85 Da - Sequence: N/A - small molecule phenothiazine (not a peptide) ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [NAD+](https://peptidelabs.app/peptides/nad/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## MGF (IGF-1 Ec) URL: https://peptidelabs.app/peptides/mgf-igf-1-ec/ Also known as: Mechano Growth Factor, IGF-1 Ec, IGF-1 splice variant Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview The IGF-1Ec splice variant and its synthetic 24-residue E-domain peptide; mRNA rises in loaded human muscle, but the peptide's proliferative effect failed to replicate and no endogenous peptide has been isolated. MGF is the name given to the IGF-1Ec splice variant (IGF-1Eb in rodents), whose mRNA rises in skeletal muscle after loading or damage; what is sold is the synthetic 24-residue C-terminal E-domain peptide. The mRNA response is documented: it rose after stretch and stimulation in rabbit muscle (McKoy 1999) and after high-resistance exercise in young but not elderly men (Hameed 2003). The peptide's own effects are contested. The original report found the E domain increased myoblast proliferation and delayed differentiation through a receptor other than IGF-1R (Yang 2002). Two pharmaceutical companies then failed to reproduce any effect on human or mouse myoblasts or muscle stem cells up to 500 ng/mL (Fornaro 2014), and no endogenous peptide matching it has been isolated from cells, medium, tissue or fluid (Matheny 2010). No human study of the peptide exists. ### Benefits Increased myoblast proliferation and delayed differentiation in vitro (contested; a two-company replication found no effect); neuroprotection in gerbil brain ischemia (animal); MGF mRNA rises in human muscle after loading, which is expression, not peptide effect. No human data for the peptide ### Dosing reference - Research dose: 200 to 500 mcg post-exercise: research-community range, no published human dose and no published animal injection dose for the peptide - Range: 200 to 500 mcg, Post-workout - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Intramuscular or subcutaneous in community use. Local injection for local growth is not established: no published study has injected this peptide into muscle in any species, and the in vitro proliferative effect itself failed to replicate at up to 500 ng/mL (Fornaro 2014). No measured half-life exists for the peptide. ### Mechanism Alternative splicing of the IGF-1 gene across exons 4, 5 and 6 yields pro-IGF-1 isoforms with different E domains; the IGF-1Ec (rodent Eb) form is upregulated by loading and damage, which is why it was named mechano growth factor (Matheny 2010). The synthetic 24-residue C-terminal E peptide was reported to increase myoblast proliferation and delay terminal differentiation, an effect that persisted when IGF-1R was blocked with an antibody, implying a separate and still unidentified receptor (Yang 2002). That proposed mechanism is disputed: a replication across two companies found no effect on proliferation, differentiation or p-ERK in myoblasts, muscle stem cells or cardiac myocytes up to 500 ng/mL, while IGF-1 and full-length IGF-1Eb worked in the same assays (Fornaro 2014). No analogous peptide product of the gene has been isolated from any biological source. ### Evidence Preclinical: animal or in vitro data only - IGF-1 splice variant mRNA including the MGF form rose after stretch and electrical stimulation in rabbit skeletal muscle (McKoy et al., 1999) - After high-resistance knee-extensor exercise, MGF mRNA rose significantly in young men (25 to 36 y, n=8) but not in elderly men (70 to 82 y, n=7); resting MGF levels were about 100-fold below IGF-1Ea (Hameed et al., 2003) - The synthetic Ec E-domain peptide increased myoblast proliferation and inhibited terminal differentiation in vitro, and the effect survived IGF-1 receptor blockade, implying a different receptor (Yang and Goldspink, 2002) - The same C-terminal peptide was neuroprotective in gerbil transient brain ischemia and in organotypic hippocampal culture, independent of the IGF-1 receptor (Dluzniewska et al., 2005) - A replication across two pharmaceutical companies found no effect of MGF peptide up to 500 ng/mL on proliferation or differentiation of human or mouse myoblasts or primary muscle stem cells, and no p-ERK activation in cardiac myocytes, while IGF-1 and full-length IGF-1Eb worked in the same assays (Fornaro et al., 2014) - Human-trial status: none. No trial of MGF peptide has been published or registered; human data are limited to mRNA expression in muscle biopsies, and no endogenous MGF peptide has been isolated from any tissue or fluid (Matheny et al., 2010) ### References - [Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. Yang SY, Goldspink G, FEBS Letters, 2002](https://doi.org/10.1016/s0014-5793(02)02918-6) - [Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise. Hameed M, Orrell RW, Cobbold M, Goldspink G, Harridge SD, The Journal of Physiology, 2003](https://doi.org/10.1113/jphysiol.2002.032136) - [Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. McKoy G, Ashley W, Mander J, et al., The Journal of Physiology, 1999](https://doi.org/10.1111/j.1469-7793.1999.0583v.x) - [A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. Dluzniewska J, Sarnowska A, Beresewicz M, et al., FASEB Journal, 2005](https://doi.org/10.1096/fj.05-3786fje) - [Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells. Fornaro M, Hinken AC, Needle S, et al., American Journal of Physiology. Endocrinology and Metabolism, 2014](https://doi.org/10.1152/ajpendo.00408.2013) - [Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Matheny RW Jr, Nindl BC, Adamo ML, Endocrinology, 2010](https://doi.org/10.1210/en.2009-1217) ### Side effects No human study of the MGF peptide exists, and no pharmacokinetic or toxicology data are published for it in any species. Localized swelling and injection-site pain are reported by users. Hypoglycemia is the risk usually cited for IGF-1 family peptides through insulin receptor cross-reactivity, but the E-domain peptide is not IGF-1 and its reported effects were IGF-1R-independent, so that concern is inferred rather than measured. Because IGF-1 signaling promotes cell proliferation, use with active or suspected malignancy is inadvisable. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured. No pharmacokinetic study of the MGF peptide has been published in any species - Molecular weight: 2868.16 Da - Sequence: YQPPSTNKNTKSQRRKGSTFEERK (24 aa, C-terminal E domain of human IGF-1Ec) ### Stacks with - [IGF-1 LR3](https://peptidelabs.app/peptides/igf-1-lr3/) - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## MK-2866 URL: https://peptidelabs.app/peptides/mk-2866/ Also known as: Ostarine, Enobosarm, GTx-024, S-22 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Enobosarm (ostarine), a non-steroidal selective androgen receptor modulator - not a peptide; human trials at 1-3 mg daily showed gains in lean body mass and physical function. MK-2866 (enobosarm, ostarine, GTx-024, S-22) is a non-steroidal selective androgen receptor modulator, not a peptide. In a 12-week phase 2 trial in 120 healthy elderly men and postmenopausal women, 3 mg daily raised total lean body mass (p<0.001) and improved stair-climb physical function and insulin resistance (Dalton 2011). In a phase 2 trial in 159 patients with cancer-related weight loss, 1 mg and 3 mg daily increased lean body mass over 113 days (median +1.5 kg and +1.0 kg) while placebo did not (Dobs 2013). The phase 3 POWER programme in non-small-cell lung cancer did not deliver an approval, and enobosarm has since been tested at 9 and 18 mg daily in AR-positive advanced breast cancer (Palmieri 2024, n=136). It is not approved anywhere, and it is on the WADA prohibited list. ### Benefits Lean body mass (human phase 2 RCTs: +1.5 kg median at 1 mg daily in cancer patients, dose-dependent gain in healthy elderly), physical function (human phase 2, 3 mg vs placebo p=0.013), insulin resistance (same trial, p=0.013). Bone and recovery claims are not from human trials. ### Dosing reference - Research dose: 1 to 3 mg orally once daily in the lean-mass trials; 9 or 18 mg daily tested in breast cancer - Range: 1000 to 3000 mcg, 1x daily Oral, once daily. Not a peptide: a non-steroidal SARM, not approved by any regulator. Lean-mass trials used 1 to 3 mg daily; oncology trials have gone to 9 and 18 mg daily (Palmieri 2024). The 15 to 25 mg range common in community protocols is above every muscle-wasting dose tested and within the breast-cancer range, where it was given under oncology monitoring. Rifampin cut enobosarm exposure by 43% (AUC) and probenecid raised it by 50% (Coss 2016). It is prohibited in sport by WADA and products sold as research chemicals are frequently mislabeled or contaminated (Vasireddi 2025). ### Mechanism Enobosarm is a non-steroidal ligand that binds the androgen receptor and acts as a tissue-selective agonist, anabolic in muscle and bone while largely sparing prostate in men and hair-growth-related tissue in women (Dalton 2011). Receptor activation in skeletal muscle drives protein synthesis and nitrogen retention, which is what the lean-body-mass gains in the phase 2 trials measure. Selectivity is relative, not absolute: human trials report dose-dependent suppression of endogenous testosterone through negative feedback on the hypothalamic-pituitary axis, along with falls in HDL and SHBG. It is cleared mainly by glucuronidation with a CYP3A4 component, which is why rifampin lowers and probenecid raises exposure (Coss 2016). It is not a peptide and is included for reference. ### Evidence Clinical: at least one published human trial or an approved drug - In 120 healthy elderly men and postmenopausal women over 12 weeks, 3 mg daily increased total lean body mass (p<0.001 vs placebo) and improved physical function and insulin resistance (both p=0.013) (Dalton et al., 2011) - In 159 patients with cancer and at least 2% weight loss, 113 days of 1 mg or 3 mg daily increased lean body mass (median +1.5 kg and +1.0 kg; placebo +0.02 kg, not significant) (Dobs et al., 2013) - The phase 3 POWER programme in non-small-cell lung cancer was designed around lean body mass and stair-climb power as co-primary endpoints; no approval followed (Crawford et al., 2016) - In AR-positive, ER-positive advanced breast cancer, 9 mg (n=72) and 18 mg (n=64) daily were given in an open-label phase 2 trial, the highest doses studied in humans (Palmieri et al., 2024) - A systematic review of SARM use in athletes found no approved indication for any SARM and case reports of drug-induced liver injury, myocarditis and tendon rupture, plus frequent product contamination (Vasireddi et al., 2025) - Human-trial status: multiple published phase 2 RCTs and a phase 3 programme; not approved by FDA, EMA or any other regulator, and prohibited in sport by WADA ### References - [Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Dobs AS, Boccia RV, Croot CC, et al., Lancet Oncology, 2013](https://pubmed.ncbi.nlm.nih.gov/23499390/) - [The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women. Dalton JT, Barnette KG, Bohl CE, et al., Journal of Cachexia, Sarcopenia and Muscle, 2011](https://pubmed.ncbi.nlm.nih.gov/21475617/) - [Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials). Crawford J, Prado CM, Johnston MA, et al., Current Oncology Reports, 2016](https://doi.org/10.1007/s11912-016-0522-0) - [Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial. Palmieri C, Linden H, Birrell SN, et al., Lancet Oncology, 2024](https://doi.org/10.1016/S1470-2045(24)00004-4) - [Pharmacokinetic drug interactions of the selective androgen receptor modulator GTx-024(Enobosarm) with itraconazole, rifampin, probenecid, celecoxib and rosuvastatin. Coss CC, Jones A, Dalton JT, Investigational New Drugs, 2016](https://doi.org/10.1007/s10637-016-0353-8) - [Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review. Vasireddi N, Hahamyan HA, Gould HP, et al., American Journal of Sports Medicine, 2025](https://doi.org/10.1177/03635465241252435) ### Side effects Human trials report dose-dependent suppression of endogenous testosterone and LH and falls in HDL cholesterol. Case reports and a 2025 systematic review of athlete SARM use document drug-induced liver injury, myocarditis and tendon rupture, with frequent mislabeling or contamination of products sold as research chemicals (Vasireddi 2025). In the cancer trial the serious adverse events were disease-related, not drug-attributed (Dobs 2013). Not approved for human use and prohibited in sport by WADA. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: Dosed once daily in every human trial; no primary human t½ measurement located (the ~24 h figure in circulation is unsourced) - Bioavailability: Oral: active orally in all human trials; the ~80% figure has no primary source - Molecular weight: 389.33 Da ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [TB-500](https://peptidelabs.app/peptides/tb-500/) ### Categories - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## MK-677 URL: https://peptidelabs.app/peptides/mk-677/ Also known as: Ibutamoren, Ibutamoren mesylate, MK-0677, L-163,191, Nutrobal Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Ibutamoren, an orally active non-peptide ghrelin receptor agonist that raises GH and IGF-1 in human trials; studied for lean mass, bone density, and sleep quality. MK-677 (ibutamoren, L-163,191) is a Merck non-peptide spiropiperidine built as an oral mimic of GHRP-6 (Patchett 1995); it is in this catalog for reference only. In 32 healthy adults aged 64-81, 25 mg daily for 4 weeks nearly doubled 24 h GH and raised IGF-1 from 141 to 265 mcg/L, with a rise in fasting glucose (Chapman 1996). A 2-year RCT in 65 older adults found fat-free mass +1.1 kg vs -0.5 kg on placebo, no change in visceral fat, weight +2.7 kg, higher fasting glucose and lower insulin sensitivity (Nass 2008). Other RCTs: more fat-free mass in obese men (Svensson 1998), reversed diet-induced nitrogen loss (Murphy 1998), more deep and REM sleep (Copinschi 1997), no effect on Alzheimer progression (Sevigny 2008), and a hip-fracture trial stopped for a heart-failure signal (Adunsky 2011). Not approved anywhere. ### Benefits Increased GH and IGF-1, lean mass gain, improved sleep quality ### Dosing reference - Research dose: 10-25 mg oral once daily (RCT doses 2-25 mg; 25 mg in most trials) - Range: 10000 to 25000 mcg, 1x daily Oral, once daily; trials dosed at bedtime (Copinschi 1997) or without timing restriction. 25 mg daily was the dose in most RCTs; 2 and 10 mg were less effective on IGF-1 (Chapman 1996). Fasting glucose rose and insulin sensitivity fell in trials of 4 weeks to 2 years (Chapman 1996; Nass 2008). Appetite increase subsided after a few months in the 2-year trial (Nass 2008). Not injectable. ### Mechanism MK-677 is an orally active non-peptide agonist of the growth hormone secretagogue receptor GHS-R1a, the ghrelin receptor, designed as a peptidomimetic of GHRP-6 (Patchett 1995). It amplifies existing pulsatile GH secretion, raising pulse height and trough levels without changing pulse number, and produces a sustained IGF-1 rise with once-daily dosing (Chapman 1996). Cortisol was unchanged in older adults (Chapman 1996) and rose only transiently after first doses in obese men (Svensson 1998); prolactin rose modestly. Appetite stimulation follows ghrelin-receptor activation. Note: not a peptide; included for reference. ### Evidence Clinical: at least one published human trial or an approved drug - 25 mg daily for 4 weeks raised IGF-1 from 141 to 265 mcg/L and 24 h GH 97% in 32 adults aged 64-81; fasting glucose rose (Chapman et al., 1996) - 2-year RCT, n=65: fat-free mass +1.1 kg vs -0.5 kg placebo, no visceral fat change, fasting glucose up, insulin sensitivity down (Nass et al., 2008) - 8 weeks of 25 mg in 24 obese men: IGF-1 +40%, fat-free mass up, impaired glucose tolerance (Svensson et al., 1998) - 7 days of 25 mg increased stage IV sleep ~50% and REM sleep >20% in young men; REM up ~50% in older adults (Copinschi et al., 1997) - Hip-fracture RCT, n=123: IGF-1 up, most function measures unchanged, terminated early for a congestive heart failure signal (Adunsky et al., 2011) - Human-trial status: multiple phase 2 RCTs 1996-2011; no clinical effect on Alzheimer progression (Sevigny et al., 2008); not approved anywhere, development discontinued ### References - [Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Patchett AA, Nargund RP, Tata JR, et al., Proceedings of the National Academy of Sciences USA, 1995](https://doi.org/10.1073/pnas.92.15.7001) - [Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. Chapman IM, Bach MA, Van Cauter E, et al., Journal of Clinical Endocrinology & Metabolism, 1996](https://doi.org/10.1210/jcem.81.12.8954023) - [Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Copinschi G, Leproult R, Van Onderbergen A, et al., Neuroendocrinology, 1997](https://doi.org/10.1159/000127249) - [Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. Svensson J, Lonn L, Jansson JO, et al., Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.2.4539) - [MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. Murphy MG, Plunkett LM, Gertz BJ, et al., Journal of Clinical Endocrinology & Metabolism, 1998](https://doi.org/10.1210/jcem.83.2.4551) - [Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Nass R, Pezzoli SS, Oliveri MC, et al., Annals of Internal Medicine, 2008](https://doi.org/10.7326/0003-4819-149-9-200811040-00003) - [MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Adunsky A, Chandler J, Heyden N, et al., Archives of Gerontology and Geriatrics, 2011](https://doi.org/10.1016/j.archger.2010.10.004) - [Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML; MK-677 Protocol 201 Study Group, Neurology, 2008](https://doi.org/10.1212/01.wnl.0000335163.88054.e7) ### Side effects Trials report increased appetite (subsiding over months), transient mild lower-extremity edema and muscle pain (Nass 2008), higher fasting glucose and reduced insulin sensitivity (Chapman 1996; Nass 2008; Svensson 1998), transient cortisol and prolactin rises after first doses (Svensson 1998), and a congestive heart failure safety signal that stopped a hip-fracture trial in elderly patients (Adunsky 2011). Lethargy, joint aches and carpal tunnel symptoms are commonly reported (anecdotal). ### Storage - Storage: Room temperature, dry, away from light (general guidance for an oral small molecule) - Lyophilized: 2+ years at room temperature (general guidance) ### Pharmacology - Half-life: Plasma half-life not located in primary literature (secondary sources cite 4-6 h); once-daily oral dosing sustains 24 h GH and IGF-1 elevation (human; Chapman 1996) - Bioavailability: Orally active in humans (Patchett 1995; Chapman 1996); no absolute bioavailability figure located - Molecular weight: 528.66 Da ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) - [Sleep](https://peptidelabs.app/peptides/category/sleep/) ## MOTS-c URL: https://peptidelabs.app/peptides/mots-c/ Also known as: Mitochondrial open reading frame of the 12S rRNA type-c, Mitochondrial-derived peptide (MDP) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Sixteen-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene; shown in animal models to activate AMPK and act as an exercise mimetic improving insulin sensitivity. MOTS-c is a 16-amino-acid microprotein encoded in a short open reading frame inside the mitochondrial 12S rRNA gene. It was described in 2015: treatment prevented age-dependent and high-fat-diet insulin resistance and diet-induced obesity in mice, with skeletal muscle as the apparent target organ and inhibition of the folate cycle and de novo purine synthesis leading to AMPK activation (Lee 2015). Injected MOTS-c improved physical performance in young, middle-aged and old mice and, started at 23.5 months, raised physical capacity late in life (Reynolds 2021). It also limited immobilisation-induced muscle atrophy in mice (Kumagai 2024). In humans only endogenous changes are documented: exercise raises MOTS-c in muscle and circulation (Reynolds 2021). A phase 2a trial in prediabetes began recruiting in 2026. ### Benefits Insulin sensitivity and reduced diet-induced obesity (mouse), physical capacity in young to old mice, protection against immobilisation muscle atrophy (mouse); exercise raises endogenous levels (human) ### Dosing reference - Research dose: 5-10 mg per injection (research-community range; rodent studies used 5-15 mg/kg/day intraperitoneally, which does not convert to a fixed human dose) - Range: 5000 to 10000 mcg, 1-3x weekly - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Community protocols use subcutaneous injection. Published dosing is rodent and intraperitoneal: 5 mg/kg three times weekly from 23.5 months of age for the healthspan work (Reynolds 2021) and 15 mg/kg/day for 8 days in the immobilisation model (Kumagai 2024). The recruiting phase 2a trial uses a fixed once-daily subcutaneous dose for 12 weeks (NCT07505745). No human pharmacokinetic data. ### Mechanism MOTS-c is encoded within the mitochondrial 12S rRNA gene and acts as a mitochondrial-derived signalling peptide. In the original report its cellular action was inhibition of the folate cycle and the de novo purine synthesis it feeds, which raises AICAR levels and activates AMPK, with skeletal muscle as the primary target organ (Lee 2015). It binds and activates casein kinase 2 in muscle (Kumagai 2024, iScience). Rodent work links treatment to PGC-1alpha expression, AMPK signalling and improved mitochondrial respiration (Yang 2021; Gudiksen 2026). Endogenous expression rises with exercise in mouse and human muscle and falls with age (Reynolds 2021). Nuclear translocation under metabolic stress is reported in cell work (Lee 2015). ### Evidence Preclinical: animal or in vitro data only - Treatment prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity in mice; target organ skeletal muscle (Lee et al., 2015) - Improved physical performance in young, middle-aged and old mice; intermittent treatment from 23.5 months raised physical capacity and healthspan (Reynolds et al., 2021) - 15 mg/kg/day for 8 days limited immobilisation-induced muscle loss in mice to 5% versus 15% in controls, with less muscle lipid infiltration (Kumagai et al., 2024) - Exercise raised endogenous MOTS-c in human skeletal muscle and circulation; levels decline with age (Reynolds et al., 2021) - Aerobic and resistance exercise changed circulating MOTS-c in breast cancer survivors (Dieli-Conwright et al., 2021); circulating mitochondrial-derived peptide levels track metabolic state in a meta-analysis (Zhou et al., 2024) - Human-trial status: no completed trial of MOTS-c itself. The analog CB4211 completed a phase 1a/1b safety and PK study (n=88, subcutaneous, CohBar, NCT03998514) and a phase 2a of MOTS-c in prediabetes with overweight or obesity began recruiting in 2026 (n=120 estimated, NCT07505745) ### References - [The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee C, Zeng J, Drew BG, et al., Cell Metabolism, 2015](https://doi.org/10.1016/j.cmet.2015.02.009) - [MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC, Lai RW, Woodhead JST, et al., Nature Communications, 2021](https://doi.org/10.1038/s41467-020-20790-0) - [Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration. Kumagai H, Kim SJ, Miller B, et al., American Journal of Physiology - Endocrinology and Metabolism, 2024](https://doi.org/10.1152/ajpendo.00285.2023) - [MOTS-c modulates skeletal muscle function by directly binding and activating CK2. Kumagai H, Kim SJ, Miller B, et al., iScience, 2024](https://doi.org/10.1016/j.isci.2024.111212) - [MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway. Yang B, Yu Q, Chang B, et al., Biochimica et Biophysica Acta - Molecular Basis of Disease, 2021](https://doi.org/10.1016/j.bbadis.2021.166126) - [Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Dieli-Conwright CM, Sami N, Norris MK, et al., Scientific Reports, 2021](https://doi.org/10.1038/s41598-021-96419-z) - [The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis. Zhou Q, Yin S, Lei X, et al., Diabetology & Metabolic Syndrome, 2024](https://doi.org/10.1186/s13098-024-01405-w) - [MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner. Gudiksen A, Hansen CC, van der Stede T, et al., Free Radical Biology and Medicine, 2026](https://doi.org/10.1016/j.freeradbiomed.2026.01.002) ### Side effects No published adverse-event data for MOTS-c in humans; the recruiting phase 2a trial is the first to collect it (NCT07505745). The analog CB4211 completed a phase 1a/1b safety study in 88 subjects, with results not published in the peer-reviewed literature (NCT03998514). Injection-site irritation and transient fatigue are commonly reported (anecdotal). Effects of repeated dosing of a mitochondrial-derived peptide in humans are uncharacterised. ### Storage - Storage: Refrigerate 2-8°C (36-46°F); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not established; no pharmacokinetic study of MOTS-c in any species located. Rodent work dosed intraperitoneally once daily or 3x weekly (Lee 2015; Reynolds 2021) - Bioavailability: No bioavailability figure published. Rodent studies dosed intraperitoneally; the analog CB4211 was given subcutaneously in a phase 1a/1b trial (NCT03998514). Exercise raises endogenous MOTS-c in human muscle and plasma (Reynolds 2021) - Molecular weight: 2174.64 Da - Sequence: MRWQEMGYIFYPRKLR ### Stacks with - [SS-31 (Elamipretide)](https://peptidelabs.app/peptides/ss-31-elamipretide/) - [Epithalon](https://peptidelabs.app/peptides/epithalon/) ### Categories - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## N-Acetyl Epithalon Amidate URL: https://peptidelabs.app/peptides/n-acetyl-epithalon-amidate/ Also known as: Ac-AEDG-NH2, N-Acetyl-Epitalon amidate, Epitalon amidate Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Acetylated, amidated analog of the pineal tetrapeptide Epitalon (Ala-Glu-Asp-Gly), modified for stability; the parent peptide is studied for telomerase activation and anti-aging effects. N-Acetyl Epithalon Amidate is a terminally modified analog of Epitalon (AEDG), acetylated at the N-terminus and amidated at the C-terminus to slow enzymatic degradation. Research on the parent peptide - largely from Khavinson's group - reports telomerase activation, telomere elongation in cell culture, and effects on neuroendocrine and antioxidant markers. No published studies test the acetylated-amidated analog itself, so claims of greater potency are extrapolation from its chemistry. ### Benefits Telomerase induction and telomere elongation, and extra population doublings in senescing human cells, both reported for the parent peptide AEDG in vitro. Nothing has been measured for this analog in any model ### Dosing reference - Research dose: 3 to 10 mg daily in 10 to 20 day cycles: vendor convention, no published dose for this analog or for the parent peptide in humans - Range: 3000 to 10000 mcg, Daily (10-20 day cycle) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 20 mg Subcutaneous or intranasal in research use. Doses and cycles are copied from Epithalon community protocols, which themselves have no published basis. The claim that the modifications allow a lower dose than the parent peptide is not tested: no potency comparison between AEDG and this analog has been published in any model. Mouse geroprotection work on the parent used 1 mcg per animal, roughly 30 to 40 mcg/kg, on 5 days a month (Anisimov 2003). ### Mechanism No study of this analog has been published, so its mechanism is inference from the parent peptide plus the chemistry of the two modifications. For the parent AEDG, telomerase induction and telomere elongation are reported in telomerase-negative human fibroblast culture (Khavinson 2003), with extra population doublings in senescing cells (Khavinson 2004) and an independent 2025 replication (Al-Dulaimi 2025). N-terminal acetylation and C-terminal amidation are standard strategies for blocking aminopeptidase and carboxypeptidase cleavage, but no measurement of stability, exposure or potency has been published for this compound or for AEDG itself, so the usual claim of improved pharmacokinetics has nothing behind it. ### Evidence Preclinical: animal or in vitro data only - Parent peptide AEDG induced telomerase catalytic subunit expression, telomerase activity and telomere elongation in telomerase-negative human fetal fibroblasts (Khavinson et al., 2003) - Parent peptide: senescing human fibroblasts treated at passage 34 elongated telomeres and completed about 10 further passages (Khavinson et al., 2004) - Parent peptide, independent replication: dose-dependent telomere lengthening through hTERT and telomerase upregulation in normal human cells, and ALT activation in cancer lines (Al-Dulaimi et al., 2025) - Parent peptide in mice: mean lifespan and total tumor incidence unchanged, with gains confined to the last decile of survivors and maximum lifespan, and a 6-fold lower leukemia incidence (Anisimov et al., 2003) - Human-trial status: nothing has been published on the acetylated and amidated analog in any species, and no trial of it or of the parent tetrapeptide is registered on ClinicalTrials.gov. Every finding above belongs to AEDG, not to this compound ### References - [Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Khavinson VKh, Bondarev IE, Butyugov AA, Bulletin of Experimental Biology and Medicine, 2003](https://doi.org/10.1023/a:1025493705728) - [Peptide promotes overcoming of the division limit in human somatic cell. Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD, Bulletin of Experimental Biology and Medicine, 2004](https://doi.org/10.1023/b:bebm.0000038164.49947.8c) - [Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Al-Dulaimi S, Thomas R, Matta S, Roberts T, Biogerontology, 2025](https://doi.org/10.1007/s10522-025-10315-x) - [Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, et al., Biogerontology, 2003](https://doi.org/10.1023/a:1025114230714) - [Overview of Epitalon: Highly Bioactive Pineal Tetrapeptide with Promising Properties. Araj SK, Brzezik J, Madra-Gackowska K, Szeleszczuk L, International Journal of Molecular Sciences, 2025](https://doi.org/10.3390/ijms26062691) ### Side effects No safety study of this analog exists in any species, so "no adverse effects reported" reflects an absence of data, not a finding. For the parent peptide, lifelong dosing in mice produced no change in food consumption, body weight or total tumor incidence (Anisimov 2003). Commonly reported by users: nasal irritation with intranasal use, injection-site irritation. FDA placed epitalon in category 2 of its compounding interim policy, citing possible immunogenicity from aggregation and peptide-related impurities and stating that it identified no safety information for the proposed route; that nomination was withdrawn and epitalon now appears in the withdrawn-nomination table of the same page, as of 2026-04-22. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured for this analog or for the parent peptide in any species. Terminal acetylation and amidation are expected to slow exopeptidase cleavage, which is a design rationale rather than a result - Bioavailability: Not measured by any route, for this analog or for the parent peptide. No comparison with Epithalon has been published - Molecular weight: 431.41 Da - Sequence: Ac-AEDG-NH2 ### Stacks with - [DSIP](https://peptidelabs.app/peptides/dsip/) - [Epithalon](https://peptidelabs.app/peptides/epithalon/) ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## N-Acetyl Selank Amidate URL: https://peptidelabs.app/peptides/n-acetyl-selank-amidate/ Also known as: Enhanced Selank, Stabilized Selank, NASA (N-Acetyl Selank Amidate) Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Acetylated, amidated analog of Selank, a tuftsin-derived heptapeptide; Russian research on the parent peptide reports anxiolytic and mild nootropic effects without sedation. N-Acetyl Selank Amidate is a terminally modified analog of Selank, itself a synthetic analog of the immunopeptide tuftsin. Russian studies of the parent peptide report anxiolytic effects attributed to GABAergic and serotonergic modulation, plus enkephalinase inhibition and immunomodulatory (IL-6, interferon) effects, without the sedation or dependence of benzodiazepines. The acetylated-amidated analog has no published trials of its own; greater stability and potency are inferred from its chemistry and reported by users. ### Benefits Cognitive support, anxiolytic ### Dosing reference - Research dose: Vendor/community range 250 to 500 mcg once or twice daily, intranasal; no published human or animal dose for this analog. - Range: 250 to 500 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Intranasal per vendors. No pharmacology has been published for the acetylated, amidated analog; data for the parent Selank do not transfer automatically. ### Mechanism No pharmacology of the acetylated, amidated form is published; claims of better stability, absorption or potency are extrapolation. For unmodified Selank, Russian work reports inhibition of enkephalin-degrading enzymes (Zozulya et al., 2001), changes in GABAergic gene expression in rodent brain (Volkova et al., 2016) and raised hippocampal BDNF after intranasal dosing in rats (Inozemtseva et al., 2008). ### Evidence Anecdotal: no peer-reviewed data - No study of N-acetyl Selank amidate in any species has been published - Unmodified Selank was studied as an anxiolytic in a Russian trial in generalized anxiety disorder and neurasthenia (n=62) (Zozulia et al., 2008) - Unmodified Selank is reviewed as a heptapeptide anxiolytic with several proposed molecular targets (Vyunova et al., 2018) - Human-trial status: none for this analog. Unmodified Selank is a registered drug in Russia (Deigin et al., 2022); that registration does not extend to the modified form ### References - [Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zozulia AA, Neznamov GG, Siuniakov TS, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2008](https://pubmed.ncbi.nlm.nih.gov/18454096/) - [Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Vyunova TV, Andreeva L, Shevchenko K, et al., Protein & Peptide Letters, 2018](https://doi.org/10.2174/0929866525666180925144642) - [The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Zozulya AA, Kost NV, Yu Sokolov O, et al., Bulletin of Experimental Biology and Medicine, 2001](https://doi.org/10.1023/a:1017979514274) - [Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Volkova A, Shadrina M, Kolomin T, et al., Frontiers in Pharmacology, 2016](https://doi.org/10.3389/fphar.2016.00031) - [Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Inozemtseva LS, Karpenko EA, Dolotov OV, et al., Doklady Biological Sciences, 2008](https://doi.org/10.1134/s0012496608040066) - [Development of Peptide Biopharmaceuticals in Russia. Deigin VI, Poluektova EA, Beniashvili AG, et al., Pharmaceutics, 2022](https://doi.org/10.3390/pharmaceutics14040716) ### Side effects Nasal irritation, mild drowsiness, and occasional dizziness are the reported effects. Safety data for this modified analog specifically is limited; the available evidence comes from unmodified Selank in Russian trials. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in any species - Bioavailability: Not measured in any species - Molecular weight: 793 Da - Sequence: Ac-Thr-Lys-Pro-Arg-Pro-Gly-Pro-NH2 (N-acetyl, C-amide) ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [Dihexa](https://peptidelabs.app/peptides/dihexa/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## N-Acetyl Semax Amidate URL: https://peptidelabs.app/peptides/n-acetyl-semax-amidate/ Also known as: Enhanced Semax, Stabilized Semax, NASMA Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Acetylated, amidated analog of Semax, a synthetic ACTH(4-10) fragment; research on the parent peptide reports BDNF/NGF upregulation and neuroprotection in stroke models. N-Acetyl Semax Amidate is a terminally modified analog of Semax, a synthetic fragment of ACTH(4-10) with the melanocortin activity removed. Studies of the parent peptide - mostly Russian, including human stroke and optic neuropathy trials - report increased BDNF and NGF expression, neuroprotection, and effects on attention and memory. The acetylated-amidated analog has no published human or animal data of its own; claims that it exceeds Semax in potency are extrapolation from its chemistry plus user reports. ### Benefits Cognitive enhancement, focus ### Dosing reference - Research dose: Vendor/community range 200 to 600 mcg once or twice daily, intranasal; no published human or animal dose for this analog. - Range: 200 to 600 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Intranasal per vendors. No pharmacology has been published for the acetylated, amidated analog; data for the parent Semax do not transfer automatically. ### Mechanism No pharmacology of the acetylated, amidated form is published. The one study of Semax N-terminal acetylation found that it changed copper(II) and zinc(II) binding and did not protect cells against Cu(II) toxicity (Magri et al., 2016). Claims that the modifications extend half-life or improve CNS penetration have no source. For unmodified Semax, intranasal dosing raised BDNF and trkB expression in rat hippocampus (Dolotov et al., 2006). ### Evidence Anecdotal: no peer-reviewed data - N-terminal acetylation of Semax altered its copper and zinc coordination and did not protect against Cu(II) toxicity in cells (Magri et al., 2016) - Unmodified Semax raised BDNF and trkB expression in rat hippocampus (Dolotov et al., 2006) - Unmodified Semax was given at 6000 mcg/day to Russian ischemic stroke patients (Gusev et al., 2018) - Human-trial status: no study of N-acetyl Semax amidate in any species. All human data are for unmodified Semax in Russian trials; Russian peptide drug registrations are reviewed in Deigin et al., 2022 ### References - [Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. Magrì A, Tabbì G, Giuffrida A, et al., Journal of Inorganic Biochemistry, 2016](https://doi.org/10.1016/j.jinorgbio.2016.08.013) - [Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Dolotov OV, Karpenko EA, Inozemtseva LS, et al., Brain Research, 2006](https://doi.org/10.1016/j.brainres.2006.07.108) - [The efficacy of semax in the tretament of patients at different stages of ischemic stroke. Gusev EI, Martynov MY, Kostenko EV, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018](https://doi.org/10.17116/jnevro20181183261-68) - [Development of Peptide Biopharmaceuticals in Russia. Deigin VI, Poluektova EA, Beniashvili AG, et al., Pharmaceutics, 2022](https://doi.org/10.3390/pharmaceutics14040716) ### Side effects Nasal irritation, headache, and overstimulation or irritability at higher doses are the reported effects. Safety data for this modified analog specifically is limited; the available evidence comes from unmodified Semax in Russian trials. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in any species - Bioavailability: Not measured in any species - Molecular weight: 855 Da - Sequence: Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2 (N-acetyl, C-amide) ### Stacks with - [Selank](https://peptidelabs.app/peptides/selank/) - [Dihexa](https://peptidelabs.app/peptides/dihexa/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## NAD+ URL: https://peptidelabs.app/peptides/nad/ Also known as: Nicotinamide Adenine Dinucleotide, Coenzyme I, DPN (diphosphopyridine nucleotide) Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Nicotinamide adenine dinucleotide, the central redox coenzyme; a 2026 randomized trial of intravenous NAD+ at 10 mg/day for 7 days raised ejection fraction in 180 ischemic cardiomyopathy patients. NAD+ is a dinucleotide coenzyme, not a peptide (PubChem CID 5892). Direct administration is studied far less than its precursors. The one randomized controlled trial gave 10 mg/day intravenously for 7 days alongside guideline therapy to 180 patients with ischemic cardiomyopathy and an ejection fraction of 45% or less: ejection fraction at 1 month was higher than placebo (45.4% versus 42.4%), while NT-proBNP, event rates and NYHA class showed trends only (Yu 2026). A pilot infusion study found that at 3 micromol/min no rise in plasma NAD+ or its metabolites appeared for the first 2 hours, implying rapid and complete removal from plasma, with NAD+ and methylnicotinamide later appearing in urine (Grant 2019). A 2026 retrospective comparison of commercial infusions found NAD+ markedly less tolerable than nicotinamide riboside. ### Benefits Higher left ventricular ejection fraction after 7 days of intravenous dosing in ischemic cardiomyopathy (human RCT, n=180), raised urinary NAD+ and methylnicotinamide excretion during infusion (human pilot, n small), improved metabolic markers in aged animals (rodent only) ### Dosing reference - Research dose: 50 to 100 mg subcutaneous or intramuscular: clinic and community range. The only randomized trial used 10 mg/day intravenously, and commercial infusion protocols use 500 mg per session - Range: 50000 to 100000 mcg, 1-3x weekly - Reconstitution: 5 mL bacteriostatic water - Common vial sizes: 100 mg, 250 mg, 500 mg Published human doses, verbatim: 10 mg/day intravenously for 7 days in the randomized cardiomyopathy trial (Yu 2026); 500 mg intravenously on four consecutive days in a commercial setting, where moderate to severe gastrointestinal symptoms, higher heart rate and chest pressure stretched mean infusion time to 97 minutes against 37 minutes for nicotinamide riboside (Reyna 2026); 3 micromol/min for 6 hours, about 720 mg total, in a pilot pharmacokinetic study (Grant 2019). Infusion rate, not total dose, drives the symptoms. Subcutaneous and intramuscular dosing has no published study at all. ### Mechanism NAD+ is the electron carrier in the NAD+/NADH couple and the substrate for sirtuin deacetylases, PARP DNA-repair enzymes and CD38. Tissue NAD+ declines with age across species, which is the rationale for repletion (Verdin 2015; Covarrubias 2021). What direct administration does is less clear. In the one published human infusion study, plasma NAD+ did not rise for 2 hours at 3 micromol/min and the metabolite profile was consistent with extracellular NAD+ glycohydrolase and pyrophosphatase activity, meaning the molecule is largely degraded before any cell takes it up intact; urinary excretion of NAD+ itself and methylnicotinamide followed (Grant 2019). Any benefit from injected NAD+ may therefore run through its breakdown products rather than through intact uptake. ### Evidence Clinical: at least one published human trial or an approved drug - Intravenous NAD+ 10 mg/day for 7 days in 180 patients with ischemic cardiomyopathy raised 1-month ejection fraction over placebo (45.4% versus 42.4%); NT-proBNP, 6-month composite events and NYHA class improvement all trended in favor without reaching significance, and ventricular dimensions did not change (Yu et al., 2026) - In a 6-hour infusion at 3 micromol/min, plasma NAD+ and its metabolites did not rise for the first 2 hours, indicating rapid and complete plasma clearance; urinary NAD+ and methylnicotinamide rose by 6 hours (Grant et al., 2019) - A retrospective comparison of 500 mg intravenous NAD+ against intravenous nicotinamide riboside over four consecutive days found moderate to severe gastrointestinal symptoms, raised heart rate and chest pressure in the NAD+ group, with no changes in liver, renal, inflammatory or thyroid markers in either (Reyna et al., 2026) - Tissue NAD+ decline with age and the resulting effects on sirtuin and PARP activity are established in animal models and reviewed extensively; the clinical translation remains at the precursor stage (Verdin et al., 2015; Covarrubias et al., 2021) - Human-trial status: one randomized placebo-controlled trial of injected NAD+ exists, in cardiology, with a surrogate primary endpoint. No trial supports use for fatigue, addiction or aging, no regulator has approved NAD+ for any indication, and openFDA returns no approved US drug product containing it ### References - [Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial. Yu X, Xu J, Cao J, Xu Q, et al., American Journal of Cardiovascular Drugs, 2026](https://doi.org/10.1007/s40256-025-00764-7) - [A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. Grant R, Berg J, Mestayer R, Braidy N, et al., Frontiers in Aging Neuroscience, 2019](https://doi.org/10.3389/fnagi.2019.00257) - [Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. Reyna K, Heinzen G, Patel N, Ritter M, et al., Frontiers in Aging, 2026](https://doi.org/10.3389/fragi.2026.1652582) - [NAD+ in aging, metabolism, and neurodegeneration. Verdin E, Science, 2015](https://doi.org/10.1126/science.aac4854) - [NAD+ metabolism and its roles in cellular processes during ageing. Covarrubias AJ, Perrone R, Grozio A, Verdin E, Nature Reviews Molecular Cell Biology, 2021](https://doi.org/10.1038/s41580-020-00313-x) - [Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Zhang J, Wang HL, Lautrup S, Nilsen HL, et al., Nature Aging, 2025](https://doi.org/10.1038/s43587-025-00947-6) ### Side effects Infusion symptoms are the dominant finding. In a retrospective comparison of 500 mg intravenous NAD+ with intravenous nicotinamide riboside, the NAD+ group reported moderate to severe gastrointestinal symptoms, raised heart rate and chest pressure during infusion, all resolving when the infusion finished, and infusions took 97 minutes on average against 37 (Reyna 2026). Liver enzymes, renal markers, hsCRP and TSH did not change in either group over 30 days. In the randomized cardiology trial at 10 mg/day no safety signal was reported (Yu 2026). Injection-site pain with subcutaneous use is commonly reported (anecdotal). Long-term safety of direct NAD+ administration is unstudied. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not formally reported. During a 6-hour infusion at 3 micromol/min, plasma NAD+ did not rise for 2 hours, which the authors read as rapid and complete removal from plasma (Grant 2019) - Bioavailability: Intravenous: does not produce a measurable plasma rise at 3 micromol/min, with the metabolite pattern pointing to extracellular degradation (Grant 2019). Subcutaneous and intramuscular: no data. Oral: not studied for NAD+ itself; the oral literature is on precursors - Molecular weight: 663.43 Da ### Stacks with - [NMN](https://peptidelabs.app/peptides/nmn/) - [Epithalon](https://peptidelabs.app/peptides/epithalon/) ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## NMN URL: https://peptidelabs.app/peptides/nmn/ Also known as: Nicotinamide Mononucleotide, β-NMN Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Nicotinamide mononucleotide, a direct oral precursor to NAD+; human trials report raised NAD+ metabolites and improved muscle insulin sensitivity in prediabetic women. NMN is a nucleotide, not a peptide: a phosphorylated form of nicotinamide riboside and the immediate precursor of NAD+ in the salvage pathway (PubChem CID 14180). Human trials are small and short. A 10-week randomized placebo-controlled trial in 25 prediabetic postmenopausal women with overweight or obesity found higher insulin-stimulated glucose disposal by hyperinsulinemic-euglycemic clamp and raised muscle AKT and mTOR phosphorylation at 250 mg/day; body weight and liver fat did not change (Yoshino 2021). A 12-week trial at 250 mg/day in 36 middle-aged adults raised serum nicotinamide and showed a non-significant trend to lower pulse wave velocity (Katayoshi 2023). Daily doses to 1250 mg for 4 weeks were tolerated in 31 healthy adults (Fukamizu 2022). No trial has measured a clinical aging outcome. ### Benefits Raised blood NAD+ metabolites at 250 mg/day (human RCT), improved muscle insulin sensitivity in prediabetic postmenopausal women (human RCT, n=25), higher oxygen uptake during training at 600 to 1200 mg/day (human RCT, n=48), reversal of age-related metabolic decline (rodent only) ### Dosing reference - Research dose: 250 to 500 mg daily, oral: the range used in the published placebo-controlled trials - Range: 250000 to 500000 mcg, 1x daily Oral capsule. Published human doses: single doses of 100, 250 and 500 mg (Irie 2020); 250 mg/day for 10 weeks (Yoshino 2021) and 12 weeks (Katayoshi 2023); 250 mg/day for 8 weeks (Yamaguchi 2024); 300, 600 and 1200 mg/day for 6 weeks in trained runners, where only the 600 and 1200 mg arms separated from placebo on oxygen uptake (Liao 2021); 1250 mg/day for 4 weeks in a safety study (Fukamizu 2022). ### Mechanism NMN is converted to NAD+ by NMNAT enzymes in the salvage pathway, and NAD+ is the substrate for sirtuins, PARPs and CD38. In humans, oral NMN raises blood NAD+ and the downstream methylated metabolites, which is the only part of the chain measured directly (Irie 2020; Katayoshi 2023; Yamaguchi 2024). Two mechanistic claims that circulate as settled are not. Direct cellular uptake through the transporter Slc12a8 was proposed in mice (Grozio 2019) and contested in the same journal, on the grounds that the reported kinetics and NMN concentrations are not physiological (Schmidt 2019); Grozio replied and the original paper carries an author correction. Sirtuin activation and the rodent findings on mitochondrial function have not been shown to follow from NMN dosing in humans. ### Evidence Clinical: at least one published human trial or an approved drug - 250 mg/day for 10 weeks raised insulin-stimulated glucose disposal and muscle AKT and mTOR phosphorylation in 25 prediabetic postmenopausal women; body weight, liver fat and blood pressure did not change (Yoshino et al., 2021) - Single oral doses of 100, 250 and 500 mg in 10 healthy men produced no clinical or laboratory signal, and plasma methylated nicotinamide metabolites rose dose-dependently over 5 h (Irie et al., 2020) - 1250 mg/day for 4 weeks in 31 healthy adults, randomized and placebo-controlled, produced no changes beyond physiological variation and no serious adverse events (Fukamizu et al., 2022) - 250 mg/day for 12 weeks in 36 healthy middle-aged adults raised serum nicotinamide; pulse wave velocity trended lower but did not separate from placebo (Katayoshi et al., 2023) - 600 and 1200 mg/day for 6 weeks raised oxygen uptake and ventilatory threshold power in 48 amateur runners, while VO2max itself did not change in any arm (Liao et al., 2021) - Human-trial status: trials are consistent in raising NAD+ metabolites and are small, short and limited to surrogate endpoints. No trial has measured a clinical aging, mortality or disease-incidence outcome, and no regulator has approved NMN for any indication ### References - [Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Yoshino M et al, Science, 2021](https://doi.org/10.1126/science.abe9985) - [Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Irie J, Inagaki E, Fujita M, Nakaya H, et al., Endocrine Journal, 2020](https://doi.org/10.1507/endocrj.EJ19-0313) - [Safety evaluation of beta-nicotinamide mononucleotide oral administration in healthy adult men and women. Fukamizu Y, Uchida Y, Shigekawa A, Sato T, et al., Scientific Reports, 2022](https://doi.org/10.1038/s41598-022-18272-y) - [Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men. Yamaguchi S, Irie J, Mitsuishi M, Uchino Y, et al., Endocrine Journal, 2024](https://doi.org/10.1507/endocrj.EJ23-0431) - [Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Katayoshi T, Uehata S, Nakashima N, Nakajo T, et al., Scientific Reports, 2023](https://doi.org/10.1038/s41598-023-29787-3) - [Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Liao B, Zhao Y, Wang D, Zhang X, et al., Journal of the International Society of Sports Nutrition, 2021](https://doi.org/10.1186/s12970-021-00442-4) - [Slc12a8 is a nicotinamide mononucleotide transporter. Grozio A, Mills KF, Yoshino J, Bruzzone S, et al., Nature Metabolism, 2019](https://doi.org/10.1038/s42255-018-0009-4) - [Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter. Schmidt MS, Brenner C, Nature Metabolism, 2019](https://doi.org/10.1038/s42255-019-0085-0) ### Side effects Short randomized trials report no adverse signal: 1250 mg/day for 4 weeks in 31 adults produced no changes beyond physiological variation and no serious adverse events (Fukamizu 2022), and single doses to 500 mg produced no symptoms or vital sign changes (Irie 2020). Reported events were mild and not more frequent than placebo; nausea, flushing and headache at higher doses come from user reports, not from the trials. Safety beyond 12 weeks has not been studied in humans, and the effect of sustained NAD+ elevation on existing tumors is unstudied. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: Not established. After single oral doses of 100 to 500 mg in healthy men, NMN itself was not the measured species; the methylated metabolites 2-PY and 4-PY rose dose-dependently and were still rising at 5 h (Irie 2020) - Bioavailability: Oral: absolute bioavailability has not been measured in humans. Oral dosing reliably raises blood NAD+ and nicotinamide metabolites (Irie 2020; Yamaguchi 2024). The Slc12a8 uptake route is a contested mouse finding, not a human one - Molecular weight: 334.22 Da ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## Nonapeptide-1 URL: https://peptidelabs.app/peptides/nonapeptide-1/ Also known as: Melanostatine 5, Melanostatine-5, Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic alpha-MSH(5-13) analog (Melanostatine 5) found in a 1994 library screen as a potent alpha-MSH receptor antagonist (IC50 11 nM); human data are limited to one combination-cream pilot. Nonapeptide-1 (Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2) was the most potent antagonist found when Lerner's group screened a 31,360-member library built on the alpha-MSH(5-13) sequence, with an IC50 of 11 nM (Jayawickreme et al., 1994). It is sold for cosmetics as Melanostatine 5. The one human study is a 46-person randomized pilot of a cream combining it with phenylethyl resorcinol, another depigmenting agent and sunscreen, versus sunscreen alone after triple-combination therapy for melasma; melanin index and severity scores did not differ significantly (Chatterjee et al., 2021). Its effect alone in human skin has not been published. ### Benefits Alpha-MSH receptor antagonism (in vitro), melasma maintenance as part of a multi-ingredient cream (human pilot RCT, not significant vs sunscreen) ### Dosing reference - Research dose: Topical only; no published study states an effective concentration of nonapeptide-1 alone. No oral or injectable dose exists. Sold as a topical brightening ingredient, usually in a dextran solution (Melanostatine 5). The combination-cream pilot does not give the peptide concentration in its abstract. ### Mechanism Proposed competitive antagonism at the alpha-MSH (melanocortin 1) receptor. In the screen that identified it, D-Trp at position 5 and Phe at position 6 were required for antagonism, which D-Phe at position 3 enhanced (Jayawickreme et al., 1994). The screen used a melanophore receptor assay; reduced cAMP, tyrosinase activity or melanin in human melanocytes treated with nonapeptide-1 alone has not been published. A 2024 study used it as a targeting ligand on silica nanoparticles carrying EGCG, so its own effect there cannot be separated (Huang et al., 2024). ### Evidence Preclinical: animal or in vitro data only - Most potent of a 31,360-peptide alpha-MSH(5-13) library: IC50 11 nM as an alpha-MSH receptor antagonist (Jayawickreme et al., 1994) - Used as the targeting ligand on EGCG-loaded silica nanoparticles that reduced melanin in UV-exposed skin cells and mice; the peptide's own share was not tested (Huang et al., 2024) - Randomized double-blind pilot, 46 melasma patients: a cream containing nonapeptide-1 plus other actives and sunscreen did not significantly beat sunscreen alone on melanin index (Chatterjee et al., 2021) - Human-trial status: no trial of nonapeptide-1 alone; the only RCT tests a multi-ingredient cream and missed significance on its main measures ### References - [Discovery and structure-function analysis of alpha-melanocyte-stimulating hormone antagonists. Jayawickreme CK, Quillan JM, Graminski GF, Lerner MR, The Journal of biological chemistry, 1994](https://pubmed.ncbi.nlm.nih.gov/7961978/) - [A randomized controlled pilot study of a proprietary combination versus sunscreen in melasma maintenance. Chatterjee M, Neema S, Rajput GR, Indian journal of dermatology, venereology and leprology, 2021](https://doi.org/10.25259/IJDVL_976_18) - [Enhanced skin benefits of EGCG loaded in nonapeptide-1-conjugated mesoporous silica nanoparticles to reverse skin photoaging. Huang ZJ, Zhou XH, Wen WQ, Huang ZT, et al., International journal of pharmaceutics, 2024](https://doi.org/10.1016/j.ijpharm.2024.124690) ### Side effects The 46-person combination-cream pilot reported no added safety problems (Chatterjee et al., 2021); no study of the peptide alone has assessed safety. Commonly reported (anecdotal): mild irritation or redness. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured; skin penetration of nonapeptide-1 has not been published - Molecular weight: 1206.52 Da - Sequence: Met-Pro-[D-Phe]-Arg-[D-Trp]-Phe-Lys-Pro-Val-NH2 ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Noopept URL: https://peptidelabs.app/peptides/noopept/ Also known as: GVS-111, Omberacetam Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Omberacetam, a synthetic dipeptide prodrug of cycloprolylglycine; Russian human and animal studies report memory benefits linked to BDNF and NGF upregulation. Noopept (omberacetam, N-phenylacetyl-L-prolylglycine ethyl ester) is a synthetic dipeptide that is metabolized to cycloprolylglycine, an endogenous neuropeptide. It is reported to be active at roughly 1000-fold lower doses than piracetam by weight, which reflects potency per milligram rather than a larger effect. Animal work shows increased NGF and BDNF expression in the hippocampus, and Russian clinical studies report improvements in mild cognitive impairment and reduced anxiety and irritability. ### Benefits Memory, learning, neuroprotection ### Dosing reference - Research dose: 10 mg twice daily by mouth (20 mg daily), the dose used in the Russian clinical studies - Range: 10000 to 20000 mcg, 2x daily Oral tablet, 10 mg twice daily for 1.5 to 2 months in the published studies (Neznamov and Teleshova, 2009; Amelin et al., 2011). Community protocols run 10 to 30 mg daily, above any tested dose at the top end. Rat work shows oral absorption with intact passage into brain, then conversion to cycloprolylglycine; human elimination is slower than in rats and varies widely between people, and no human metabolites were detectable at the clinical dose (Boiko et al., 2004; Boyko et al., 2018). N/A-by-design: oral tablet, so reconstitution fields are null. ### Mechanism Noopept (ethyl N-phenylacetyl-L-prolylglycinate, GVS-111) is a synthetic dipeptide ester designed as a topological analog of piracetam's beta-turn (Gudasheva et al., 2018). In rats it is absorbed orally, crosses the blood-brain barrier intact and is converted to cyclo-L-prolylglycine, an endogenous peptide with a similar activity profile (Boyko et al., 2018; Gudasheva et al., 2018). Acute dosing raised NGF and BDNF mRNA in rat hippocampus, and 28-day dosing did not produce tolerance (Ostrovskaya et al., 2008). In HEK293 reporter assays it increased DNA binding of HIF-1 and of no other transcription factor tested, which its developers propose as the primary mechanism (Vakhitova et al., 2016). Elimination is slower in humans than in rats or rabbits and varies widely between individuals, with no metabolites detectable in human plasma at the clinical dose (Boiko et al., 2004). ### Evidence Clinical: at least one published human trial or an approved drug - Acute dosing raised NGF and BDNF mRNA in rat hippocampus; 28 days of dosing potentiated rather than blunted the effect (Ostrovskaya et al., 2008) - Randomised comparison against piracetam in mild cognitive disorders of vascular and post-traumatic origin reported comparable or better cognitive scores on 10 mg twice daily (Neznamov and Teleshova, 2009) - Open 12-month study in 60 patients after stroke reported improved MMSE and verbal association scores after 2 months on 20 mg daily (Amelin et al., 2011) - Increased DNA binding of HIF-1 in a reporter assay and of no other transcription factor tested (Vakhitova et al., 2016) - Elimination is slower in humans than in rats or rabbits and highly variable between individuals, with no human plasma metabolites at the clinical dose (Boiko et al., 2004; Boyko et al., 2018) - Human-trial status: registered and marketed in Russia as 10 mg tablets after trials in mild cognitive impairment (Gudasheva et al., 2018). No approval elsewhere; US market surveillance found it sold undeclared in supplements at up to 40.6 mg per serving (Cohen et al., 2021) ### References - [Noopept stimulates the expression of NGF and BDNF in rat hippocampus. Ostrovskaya RU, Gudasheva TA, Zaplina AP, et al., Bulletin of Experimental Biology and Medicine, 2008](https://doi.org/10.1007/s10517-008-0297-x) - [Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin. Neznamov GG, Teleshova ES, Neuroscience and Behavioral Physiology, 2009](https://doi.org/10.1007/s11055-009-9128-4) - [Noopept in the treatment of mild cognitive impairment in patients with stroke. Amelin AV, Iliukhina AIu, Shmonin AA, Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2011](https://pubmed.ncbi.nlm.nih.gov/22500312/) - [Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept. Vakhitova YV, Sadovnikov SV, Borisevich SS, et al., Acta Naturae, 2016](https://pubmed.ncbi.nlm.nih.gov/27099787/) - [Pharmacokinetics of noopept and its active metabolite cycloprolyl glycine in rats. Boyko SS, Zherdev VP, Shevchenko RV, Biomeditsinskaya Khimiya, 2018](https://doi.org/10.18097/PBMC20186405455) - [Novel Technologies for Dipeptide Drugs Design and their Implantation. Gudasheva TA, Ostrovskaya RU, Seredenin SB, Current Pharmaceutical Design, 2018](https://doi.org/10.2174/1381612824666181008105641) - [Five Unapproved Drugs Found in Cognitive Enhancement Supplements. Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I, Neurology: Clinical Practice, 2021](https://doi.org/10.1212/CPJ.0000000000000960) - [Interspecies differences of noopept pharmacokinetics. Boiko SS, Korotkov SA, Zherdev VP, et al., Eksperimentalnaya i Klinicheskaya Farmakologiya, 2004](https://pubmed.ncbi.nlm.nih.gov/15079908/) ### Side effects Headache, irritability, and sleep disturbance are the commonly reported effects, particularly at higher doses, and some users report brain fog on abrupt discontinuation. It was well tolerated in Russian clinical trials but has no independent long-term safety data and is not approved outside Russia. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: Not quantified in humans; elimination is slower in humans than in rats or rabbits and varies widely between individuals (Boiko et al., 2004) - Bioavailability: Orally absorbed with intact passage across the blood-brain barrier in rats (Boyko et al., 2018); no human bioavailability figure published, and no sublingual data exist - Molecular weight: 318.37 Da - Sequence: N-phenylacetyl-Pro-Gly ethyl ester (synthetic dipeptide ester, PubChem CID 180496) ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [Selank](https://peptidelabs.app/peptides/selank/) - [Dihexa](https://peptidelabs.app/peptides/dihexa/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Orexin A URL: https://peptidelabs.app/peptides/orexin-a/ Also known as: Hypocretin-1, OX-A Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Hypothalamic neuropeptide (hypocretin-1) acting at OX1R and OX2R to promote wakefulness and arousal; intranasal delivery studied in sleep-deprived primates and narcolepsy models. Orexin A (hypocretin-1) is a 33-residue hypothalamic neuropeptide acting at the OX1R and OX2R receptors, identified in 1998 (Sakurai et al., 1998; de Lecea et al., 1998). Loss of orexin neurons causes narcolepsy type 1 (Peyron et al., 2000). It crosses the blood-brain barrier from blood by simple diffusion in mice, unlike orexin B (Kastin and Akerstrom, 1999). Intranasal and intravenous dosing improved cognitive performance in sleep-deprived monkeys (Deadwyler et al., 2007). In two small placebo-controlled crossover trials in narcolepsy, 435 nmol intranasally stabilised REM sleep and cut attention errors without increasing wakefulness (Baier et al., 2011; Weinhold et al., 2014), and 500 nmol raised sympathetic nerve activity in healthy men (Meusel et al., 2022). There is no approved orexin peptide product. ### Benefits Wakefulness, Arousal, Sleep regulation ### Dosing reference - Research dose: 15 to 30 mcg intranasal (community range; published human intranasal doses were 435 nmol, about 1.5 mg, and 500 nmol, about 1.8 mg) - Range: 15 to 30 mcg, As needed - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 0.5 mg Human trials used single intranasal doses of 435 nmol, about 1.5 mg, in narcolepsy with cataplexy (Baier et al., 2011; Weinhold et al., 2014) and 500 nmol, about 1.8 mg, in healthy men (Meusel et al., 2022). That is roughly fifty times the 15 to 30 mcg community figure in the numeric fields. The monkey study used 2.5 to 10 mcg/kg intravenously and an estimated 1 mcg/kg nasally (Deadwyler et al., 2007). Measured effects in healthy men were a rise in muscle sympathetic nerve activity with no change in blood pressure or heart rate (Meusel et al., 2022). Orexin A crosses the blood-brain barrier from blood by diffusion in mice, so other routes are not inert (Kastin and Akerstrom, 1999). ### Mechanism Orexin A (hypocretin-1) is produced by lateral hypothalamic neurons and binds OX1R and OX2R, G-protein-coupled receptors that drive arousal, feeding and autonomic tone (Sakurai et al., 1998; de Lecea et al., 1998). Absence of the peptide in the brain is the lesion behind narcolepsy type 1 with cataplexy (Peyron et al., 2000). Orexin A is lipophilic and enters mouse brain from blood by non-saturable diffusion, reaching parenchyma largely intact, while orexin B is degraded in blood (Kastin and Akerstrom, 1999). Intranasal delivery in humans reproduces central effects: reduced and stabilised REM sleep in narcolepsy (Baier et al., 2011) and increased muscle sympathetic nerve activity without a change in blood pressure or baroreflex sensitivity in healthy men, which the authors read as an upward reset of the vascular baroreflex set point (Meusel et al., 2022). ### Evidence Clinical: at least one published human trial or an approved drug - Orexin A and B and their receptors were identified as hypothalamic neuropeptides regulating feeding (Sakurai et al., 1998; de Lecea et al., 1998) - Narcolepsy type 1 brains show a generalised absence of hypocretin peptides, which established the deficiency as the cause (Peyron et al., 2000) - Intravenous orexin A crosses the mouse blood-brain barrier by simple diffusion, mostly intact; orexin B is degraded in blood and does not (Kastin and Akerstrom, 1999) - In sleep-deprived rhesus monkeys, both intravenous (2.5 to 10 mcg/kg) and nasal delivery improved delayed match-to-sample performance, with nasal more effective than the highest intravenous dose (Deadwyler et al., 2007) - Two placebo-controlled crossover trials in narcolepsy with cataplexy (n=8 and n=14) gave 435 nmol intranasally: REM sleep was reduced and stabilised with fewer direct wake-to-REM transitions, and attention errors fell, but nocturnal wakefulness and daytime sleepiness did not improve (Baier et al., 2011; Weinhold et al., 2014) - Human-trial status: small crossover trials only. Intranasal orexin A at 500 nmol raised resting muscle sympathetic nerve activity in 10 healthy men (Meusel et al., 2022), and daytime sleepiness did not improve in any published trial (Weinhold et al., 2014). No approval anywhere; development has moved to small-molecule orexin receptor agonists ### References - [Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Sakurai T, Amemiya A, Ishii M, et al., Cell, 1998](https://doi.org/10.1016/S0092-8674(00)80949-6) - [The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. de Lecea L, Kilduff TS, Peyron C, et al., Proceedings of the National Academy of Sciences, 1998](https://doi.org/10.1073/pnas.95.1.322) - [A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Peyron C, Faraco J, Rogers W, et al., Nature Medicine, 2000](https://doi.org/10.1038/79690) - [Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. Kastin AJ, Akerstrom V, Journal of Pharmacology and Experimental Therapeutics, 1999](https://pubmed.ncbi.nlm.nih.gov/10087007/) - [Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. Deadwyler SA, Porrino L, Siegel JM, Hampson RE, Journal of Neuroscience, 2007](https://doi.org/10.1523/JNEUROSCI.3878-07.2007) - [Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. Baier PC, Hallschmid M, Seeck-Hirschner M, et al., Sleep Medicine, 2011](https://doi.org/10.1016/j.sleep.2011.06.015) - [The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Weinhold SL, Seeck-Hirschner M, Nowak A, et al., Behavioural Brain Research, 2014](https://doi.org/10.1016/j.bbr.2013.12.045) - [Intranasal orexin A modulates sympathetic vascular tone: a pilot study in healthy male humans. Meusel M, Voss J, Krapalis A, et al., Journal of Neurophysiology, 2022](https://doi.org/10.1152/jn.00452.2021) ### Side effects In the published human trials (n=8, n=14 and n=10) intranasal dosing was tolerated with no serious adverse events reported. The measured physiological effect in healthy men was a rise in resting muscle sympathetic nerve activity, with blood pressure, heart rate and heart rate variability unchanged (Meusel et al., 2022). Beyond those single doses there is no human safety data: no repeat-dose study, no pharmacokinetics and no long-term follow-up. Orexin signalling drives arousal and autonomic tone, so cardiovascular and anxiety effects are plausible class effects rather than observed ones. ### Storage - Storage: Frozen (-20°C) - Lyophilized: 12+ months - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in humans; in mice, intravenous orexin A enters brain intact and leaves at the same rate as an albumin marker (Kastin and Akerstrom, 1999) - Bioavailability: Not quantified by any route. Intranasal dosing produces central effects in humans and monkeys (Baier et al., 2011; Deadwyler et al., 2007), and intravenous orexin A crosses the mouse blood-brain barrier by simple diffusion (Kastin and Akerstrom, 1999). - Molecular weight: 3561.1 Da - Sequence: QPLPDCCRQKTCSCRLYELLHGAGNHAAGILTL-NH2 (33 residues from HCRT, UniProt O43612, residues 34-66; pyroglutamyl N-terminus, two intrachain disulfide bonds, C-terminal amide) ### Categories - [Sleep](https://peptidelabs.app/peptides/category/sleep/) - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) ## Orforglipron URL: https://peptidelabs.app/peptides/orforglipron/ Also known as: LY3502970, OWL833, Foundayo Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Small-molecule, non-peptide oral GLP-1 receptor agonist; approved by the FDA in April 2026 as Foundayo for weight management after 72-week phase 3 trials (11.2% loss at the top dose). Orforglipron (LY3502970, OWL833) is a non-peptide GLP-1 receptor agonist reported by Chugai and Eli Lilly researchers (Kawai 2020). It is taken as a once-daily tablet with or without food. In a 36-week phase 2 trial (n=272) weight fell 9.4 to 14.7% vs 2.3% with placebo (Wharton 2023). Phase 3 ATTAIN-1 (n=3127, no diabetes) reported 7.5%, 8.4% and 11.2% loss at 6, 12 and 36 mg vs 2.1% at 72 weeks (Wharton 2025); ATTAIN-2 in type 2 diabetes reported smaller losses (Horn 2026), and ACHIEVE-1 lowered HbA1c by 1.24 to 1.48 points at 40 weeks (Rosenstock 2025). The FDA approved it on 1 April 2026 (NDA 220934, Foundayo, Eli Lilly, prescription, marketed) for weight reduction and maintenance in adults with obesity, or overweight with a weight-related condition. Labeled strengths (0.8 to 17.2 mg) differ from trial doses because the tablet is a new formulation. ### Benefits Weight loss (human phase 3 RCTs, approved indication), lower HbA1c in type 2 diabetes (human phase 3 RCT), lower waist circumference, systolic blood pressure and triglycerides (human phase 3 RCT), once-daily oral dosing without food or water restrictions (label) ### Dosing reference - Research dose: 0.8 mg once daily for at least 30 days, then 2.5 mg, then 5.5 mg, with optional steps to 9, 14.5 or 17.2 mg (FDA label, Foundayo tablets; maximum 17.2 mg). Trials used an investigational formulation at 3 to 45 mg - Range: 800 to 17200 mcg, 1x daily Oral tablet, once daily, with or without food, swallowed whole. The label escalates in steps of at least 30 days and caps the dose at 9 mg with a strong CYP3A4 inhibitor. After 7 or more missed doses the label restarts escalation at a lower dose. Because delayed gastric emptying may lower oral contraceptive absorption, the label calls for a non-oral or added barrier method for 30 days after starting and after each increase. Trial doses of the investigational formulation (6, 12, 36 mg) correspond to labeled 5.5, 9 and 17.2 mg. ### Mechanism Orforglipron is a partial agonist of the GLP-1 receptor, biased toward G-protein signalling over beta-arrestin recruitment. A cryo-EM structure shows it in a pocket of the upper helical bundle formed by the extracellular domain, extracellular loop 2 and transmembrane helices 1, 2, 3 and 7, a different binding mode from peptide agonists. Contact with the primate-specific Trp33 makes its activity species-selective, so efficacy work used humanized-receptor mice and monkeys (Kawai 2020). In people it reduces food intake, delays gastric emptying (most after the first dose) and lowers fasting glucose (label; Pratt 2023). It is cleared mainly by hepatic CYP3A4 and excreted in faeces, so strong CYP3A4 inhibitors and inducers change exposure (label). ### Evidence Clinical: at least one published human trial or an approved drug - Phase 1a, healthy adults (n=92): half-life 24.6 to 35.3 h after one dose and 48.1 to 67.5 h after 28 days; up to 5.4 kg lost in 4 weeks vs 2.4 kg with placebo (Pratt et al., 2023) - Phase 2 obesity, 36 weeks (n=272): -9.4% to -14.7% across 12 to 45 mg vs -2.3% with placebo; GI events led 10 to 17% to stop (Wharton et al., 2023) - Phase 3 ACHIEVE-1, early type 2 diabetes, 40 weeks (n=559): HbA1c -1.24 to -1.48 points vs -0.41 with placebo; weight -4.5% to -7.6% (Rosenstock et al., 2025) - Phase 3 ATTAIN-1, obesity without diabetes, 72 weeks (n=3127): -7.5% (6 mg), -8.4% (12 mg), -11.2% (36 mg) vs -2.1% with placebo (Wharton et al., 2025) - Phase 3 ATTAIN-2, obesity with type 2 diabetes, 72 weeks (n=1613): -5.1% at 6 mg, larger at higher doses, vs -2.5% with placebo (Horn et al., 2026) - Human-trial status: approved by the FDA on 2026-04-01 (Foundayo, NDA 220934, Eli Lilly) for weight management; prescription, marketed. Further phase 3 trials (ACHIEVE, ATTAIN-MAINTAIN, sleep apnoea, hypertension) continue ### References - [Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Kawai T, Sun B, Yoshino H, et al., Proceedings of the National Academy of Sciences of the USA, 2020](https://doi.org/10.1073/pnas.2014879117) - [Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants. Pratt E, Ma X, Liu R, et al., Diabetes, Obesity and Metabolism, 2023](https://doi.org/10.1111/dom.15184) - [Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. Wharton S, Blevins T, Connery L, et al., New England Journal of Medicine, 2023](https://doi.org/10.1056/NEJMoa2302392) - [Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. Rosenstock J, Hsia S, Nevarez Ruiz L, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2505669) - [Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. Wharton S, Aronne LJ, Stefanski A, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2511774) - [Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Horn DB, Ryan DH, Kis SG, et al., The Lancet, 2026](https://doi.org/10.1016/S0140-6736(25)02165-8) ### Side effects In the pooled 72-week weight trials (3155 on drug), nausea affected 26 to 35% vs 10% on placebo, with constipation, diarrhoea, vomiting, dyspepsia and abdominal pain also common; GI events led 3 to 6% to stop vs 0.7% (FDA label). Boxed warning for thyroid C-cell tumours, a rodent finding with GLP-1 agonists of unknown human relevance; contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Other label warnings: pancreatitis, severe GI reactions, acute kidney injury from volume loss, hypoglycaemia with insulin or secretagogues, diabetic retinopathy complications, gallbladder disease and aspiration under anaesthesia. ### Storage - Storage: Room temperature, 20 to 25°C, excursions 15 to 30°C (FDA label, tablets in bottles with desiccant) - Lyophilized: Not stated in the label; manufacturer expiry date applies ### Pharmacology - Half-life: 29 to 49 h (human, oral, FDA label); 24.6 to 35.3 h single dose and 48.1 to 67.5 h at day 28 (healthy adults, phase 1a) - Bioavailability: 77% absolute (human, oral 0.8 mg tablet); tmax 4 to 8 h; food lowers AUC by 19%, not clinically relevant (FDA label) - Molecular weight: 883 Da ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## OS-01 URL: https://peptidelabs.app/peptides/os-01/ Also known as: Peptide 14, Pep 14, OneSkin peptide Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Topical decapeptide (ETAKHWLKGI-NH2, Peptide 14) from OneSkin that lowered senescence markers in human skin models; two small developer-run RCTs reported better skin barrier function. OS-01, also called Peptide 14, is a 10-residue amidated peptide found by OneSkin through a screen for compounds that reduce senescence in progeria and aged fibroblasts (Zonari et al., 2023). In human skin explants a 0.01% formulation lowered senescence and SASP markers, thickened the epidermis and reduced a DNA methylation age estimate. It is senomorphic: it did not change apoptosis genes or cell counts, so it does not kill senescent cells. Human data come from OneSkin trials: a split-face, vehicle-controlled study in 22 people (Zonari et al., 2024), a 60-woman randomized trial against a commercial moisturizer (Zonari et al., 2025) and an uncontrolled eye-cream study in 22 people. Every paper has OneSkin founders as authors, and independent replication is lacking. ### Benefits Improved skin barrier function and lower TEWL (human RCTs, topical, developer-run), less periorbital wrinkle indentation versus vehicle (human RCT, n=22), lower senescence markers and DNA methylation age (ex vivo human skin), reduced senescence burden (fibroblasts, in vitro) ### Dosing reference - Research dose: Topical. 0.01% w/v in the ex vivo formulation; the clinical products' concentrations are not stated in the abstracts. A 1 mM solution (about 0.12%) was used for patch testing. Topical only. The 60-person trial applied a body formulation twice daily for 12 weeks; the eye-cream study used a dime-sized amount twice daily for 12 weeks. The ex vivo work used 0.01% w/v, and the eye cream is described as holding a higher concentration than earlier formulations. ### Mechanism Senomorphic, not senolytic. In fibroblasts Peptide 14 reduced the share of cells reaching late senescence, apparently by arresting the cell cycle and enhancing DNA repair, and the authors link this to modulation of a PP2A subunit and PP2A/AKT signaling (Zonari et al., 2023). The same paper found no change in apoptosis or autophagy genes, which contradicts the old claim of selective apoptosis of senescent cells. In immune cells in vitro it shifted PBMCs toward a Th2/Treg profile with more IL-10 and pushed macrophages toward an M2-like state (Alencar-Silva et al., 2024). The mechanism work is cell culture and explants, all from the developer's group or collaborators. ### Evidence Clinical: at least one published human trial or an approved drug - Split-face, double-blind, vehicle-controlled study, 22 participants, 12 weeks: lower TEWL than vehicle and less periorbital wrinkle indentation on the OS-01 side (Zonari et al., 2024) - Randomized, double-blind trial in 60 women aged 60 to 90 versus a commercial moisturizer, 12 weeks: better barrier function and hydration, and lower blood IL-8 (Zonari et al., 2025) - In ex vivo aged human skin, 0.01% topical formulation lowered senescence and SASP markers and DNA methylation age; in fibroblasts, reduced senescence without killing cells (Zonari et al., 2023) - Mostly non-toxic to fibroblasts and keratinocytes up to 100 uM; negative Ames, micronucleus and karyotype tests; no reactions in a 54-person patch test at 1 mM (Zonari et al., 2022) - Human-trial status: two small randomized trials and one uncontrolled study, all run by the developer (OneSkin); no independent trial ### References - [Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models. Zonari A, Brace LE, Al-Katib K, Porto WF, et al., npj aging, 2023](https://doi.org/10.1038/s41514-023-00109-1) - [In vitro and in vivo toxicity assessment of the senotherapeutic Peptide 14. Zonari A, Brace LE, Alencar-Silva T, Porto WF, et al., Toxicology reports, 2022](https://doi.org/10.1016/j.toxrep.2022.07.018) - [Double-blind, vehicle-controlled clinical investigation of peptide OS-01 for skin rejuvenation. Zonari A, Brace LE, Harder NHO, Harker C, et al., Journal of cosmetic dermatology, 2024](https://doi.org/10.1111/jocd.16242) - [OS-01 Peptide Topical Formulation Improves Skin Barrier Function and Reduces Systemic Inflammation Markers: A Pilot 12-Week Clinical Trial. Zonari A, Brace LE, Buhrer LB, Harder NHO, et al., Journal of cosmetic dermatology, 2025](https://doi.org/10.1111/jocd.70169) - [Clinical efficacy of OS-01 peptide formulation in reducing the signs of periorbital skin aging. Zonari A, Brace LE, Li F, Harder NHO, et al., International journal of cosmetic science, 2025](https://doi.org/10.1111/ics.13042) - [Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro. Alencar-Silva T, Barcelos SM, Silva-Carvalho A, Sousa MGDC, et al., Cells, 2024](https://doi.org/10.3390/cells13100813) ### Side effects No visible reactions in a repeated insult patch test with 1 mM peptide (n=54); negative Ames, micronucleus and karyotype tests; slight reduction in MeWo and HeLa cancer cell proliferation in vitro (Zonari et al., 2022). In the 60-woman trial, 3 of 30 in the OS-01 group withdrew with moderate skin reactions (rash, pimples, dry patches), possibly from the product or the supplied cleanser (Zonari et al., 2025). Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Up to 2% of the applied peptide reached the dermis of ex vivo human skin from the test formulation (Zonari et al., 2023); no systemic exposure data - Molecular weight: 1181.39 Da - Sequence: Glu-Thr-Ala-Lys-His-Trp-Leu-Lys-Gly-Ile-[NH2] ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## Ovagen URL: https://peptidelabs.app/peptides/ovagen/ Also known as: EDL, Glu-Asp-Leu, T-35 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tripeptide (EDL); despite the name, its published work is on kidney: it protected rat kidneys in toxic and ischemic injury models. Ovagen is a synthetic tripeptide (EDL, Glu-Asp-Leu) from the St. Petersburg Institute of Bioregulation and Gerontology. It is not an ovarian peptide. The developer lists it as a nephroprotector and a hepatoprotector; the hepatoprotector label cites a patent application, not a study (Khavinson 2022). The published work is renal: EDL prevented oliguria and azotemia and cut proteinuria in rats with gentamicin nephropathy and kidney ischemia-reperfusion (Zamorskii 2017) and normalized kidney function in cisplatin-induced acute renal failure (Zamorskii 2015). In aging renal cell cultures it acted on MMP-14 (Khavinson 2014). No human trial has been published. ### Benefits Kidney protection in gentamicin, cisplatin and ischemia-reperfusion injury models (rat), renal cell aging markers (in vitro) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection; vial size (20 mg) is not a dose. No published abstract states a dose in any species. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed. In rat kidney injury models EDL prevented the fall in antioxidant enzyme activity, suppressed lipid peroxidation and normalized energy supply to kidney cells (Zamorskii 2017). In aging primary kidney cell cultures it acted on the gelatinase MMP-14 (Khavinson 2014). The developer's review lists DNA binding among its effects (Khavinson 2021). The old text, which described follicle and estrogen regulation in ovarian cells, has no published source. ### Evidence Preclinical: animal or in vitro data only - Prevented oliguria and azotemia, lowered proteinuria and preserved antioxidant enzymes in rats with gentamicin nephropathy and kidney ischemia-reperfusion (Zamorskii et al., 2017) - Normalized diuresis, creatinine excretion and glomerular filtration in rats with cisplatin-induced acute renal failure (Zamorskii et al., 2015) - Acted on MMP-14 in primary kidney cell cultures during in vitro aging (Khavinson et al., 2014) - The developer's 2021 systematic review lists EDL (Ovagen) for renal function and hepatoprotection (Khavinson et al., 2021) - Human-trial status: no published human study; no study on ovarian or reproductive tissue exists ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Peptide Regulation of Gene Expression: A Systematic Review. Khavinson VK, Popovich IG, Linkova NS, Mironova ES, et al., Molecules, 2021](https://doi.org/10.3390/molecules26227053) - [Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different Genesis. Zamorskii II, Shchudrova TS, Lin'kova NS, Nichik TE, et al., Bulletin of Experimental Biology and Medicine, 2017](https://doi.org/10.1007/s10517-017-3811-1) - [Peptides Restore Functional State of the Kidneys During Cisplatin-Induced Acute Renal Failure. Zamorskii II, Shchudrova TS, Lin'kova NS, Nichik TE, et al., Bulletin of Experimental Biology and Medicine, 2015](https://doi.org/10.1007/s10517-015-3062-y) - [Peptides regulate expression of signaling molecules in kidney cell cultures during in vitro aging. Khavinson VKh, Lin'kova NS, Polyakova VO, Durnova AO, et al., Bulletin of Experimental Biology and Medicine, 2014](https://doi.org/10.1007/s10517-014-2540-y) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. The rat kidney studies report no nephrotoxicity (Zamorskii 2017). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species - Molecular weight: 375.37 Da - Sequence: EDL (Glu-Asp-Leu) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Oxytocin URL: https://peptidelabs.app/peptides/oxytocin/ Also known as: OT, Pitocin, Syntocinon Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Posterior-pituitary nonapeptide hormone; IV or IM oxytocin (Pitocin and generics) is approved by the FDA for labor induction and postpartum bleeding. Intranasal social-behavior results are mixed. Oxytocin is a nine-residue hypothalamic hormone released from the posterior pituitary. Synthetic oxytocin injection (Pitocin, NDA 018261, and several generics) is marketed in the US for intravenous induction or augmentation of labor with a medical indication and for intravenous or intramuscular control of postpartum bleeding; the label excludes elective induction. The only US intranasal product, Syntocinon nasal spray (NDA 012285), is discontinued. Intranasal research grew from small experiments such as increased trust in an investment game (Kosfeld 2005), but the largest trial, 290 children with autism over 24 weeks, found no improvement in social withdrawal (Sikich 2021). ### Benefits Uterine contraction for medically indicated labor induction and postpartum bleeding (FDA-labeled, IV/IM), increased trust in an economic game (single small human study), no effect on social withdrawal in autism (RCT, n=290) ### Dosing reference - Research dose: Community range 10 to 50 IU intranasal; research studies used 24 to 40 IU single doses. Obstetric IV/IM use follows the Pitocin label. - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Research intranasal studies typically use 24-40 IU as a single dose. Contraindicated in pregnancy outside obstetric supervision (uterine contractions). Repeated or high parenteral dosing carries hyponatremia/water-intoxication risk; can blunt blood pressure and cause flushing. Behavioral effects in trials are small and context-dependent. ### Mechanism Oxytocin acts on oxytocin receptors in the myometrium and raises intracellular calcium, driving actomyosin contraction through myosin light-chain kinase; receptor density rises sharply in pregnancy and peaks in early labor at term, so the uterine response varies widely between patients (Pitocin label). It differs from vasopressin at two of eight residues, which explains its pressor and antidiuretic effects at large doses (Pitocin label). Plasma oxytocin during infusion was measured against spontaneous labor (Fuchs 1983; Seitchik 1984). Central effects on social behavior are proposed from receptor distribution and intranasal studies in humans, with inconsistent results (Heinrichs 2009; Sikich 2021). ### Evidence Clinical: at least one published human trial or an approved drug - Oxytocin infusion for dysfunctional labor: clinical outcomes of augmentation (Seitchik and Castillo, 1982) - Plasma oxytocin pharmacokinetics measured during labor augmentation, the basis of the label's low starting infusion rate (Seitchik et al., 1984) - Plasma oxytocin in spontaneous versus oxytocin-induced labor at term; the label states infusion up to 6 mU/min matches spontaneous-labor levels (Fuchs et al., 1983) - A single intranasal dose increased trust in an investment game in healthy men (Kosfeld et al., 2005) - Intranasal oxytocin daily for 24 weeks in 290 children and adolescents with autism did not improve social withdrawal versus placebo (Sikich et al., 2021) - Human-trial status: injectable oxytocin is approved by the FDA and marketed for obstetric use; no intranasal product is approved in the US (Syntocinon nasal spray discontinued), and intranasal social-cognition findings have not held up in the largest RCT ### References - [Oxytocin augmentation of dysfunctional labor. I. Clinical data. Seitchik J, Castillo M, American Journal of Obstetrics and Gynecology, 1982](https://doi.org/10.1016/0002-9378(82)90181-8) - [Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics. Seitchik J, Amico J, Robinson AG, Castillo M, American Journal of Obstetrics and Gynecology, 1984](https://doi.org/10.1016/s0002-9378(84)90355-7) - [Oxytocin and initiation of human parturition. III. Plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha in spontaneous and oxytocin-induced labor at term. Fuchs AR, Goeschen K, Husslein P, et al., American Journal of Obstetrics and Gynecology, 1983](https://pubmed.ncbi.nlm.nih.gov/6638091/) - [Oxytocin increases trust in humans. Kosfeld M, Heinrichs M, Zak PJ, et al., Nature, 2005](https://doi.org/10.1038/nature03701) - [Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder. Sikich L, Kolevzon A, King BH, et al., New England Journal of Medicine, 2021](https://doi.org/10.1056/NEJMoa2103583) - [Oxytocin, vasopressin, and human social behavior. Heinrichs M, von Dawans B, Domes G, Frontiers in Neuroendocrinology, 2009](https://doi.org/10.1016/j.yfrne.2009.05.005) ### Side effects Pitocin label, maternal: anaphylaxis, nausea, vomiting, cardiac arrhythmia and premature ventricular contractions, hypertensive episodes, subarachnoid hemorrhage, postpartum hemorrhage, pelvic hematoma, fatal afibrinogenemia and uterine rupture. Excess dose causes uterine hypertonicity or tetanic contraction. Slow infusion over 24 hours has caused severe water intoxication with seizures, coma and death, from its antidiuretic effect. Fetal or neonatal: bradycardia, arrhythmia, low Apgar scores, jaundice, retinal hemorrhage, seizures, brain damage and death. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Plasma 1 to 6 min (human, IV), shorter in late pregnancy and lactation; uterine response fades within 1 h after IV, lasts 2 to 3 h after IM (Pitocin label) - Bioavailability: Approved routes are IV infusion and IM injection; oxytocin distributes through extracellular fluid and small amounts probably reach the fetus (Pitocin label). No US intranasal product exists, and no label gives an intranasal or CNS figure. - Molecular weight: 1007.19 Da - Sequence: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 (disulfide bridge Cys1-Cys6) ### Stacks with - [PT-141](https://peptidelabs.app/peptides/pt-141/) - [Melanotan II](https://peptidelabs.app/peptides/melanotan-ii/) ### Categories - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) ## P21 (P021) URL: https://peptidelabs.app/peptides/p21-p021/ Also known as: P021 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview P021, a CNTF-derived peptide (Ac-DGGL plus an adamantylated glycine, amide) that improved memory and neurogenesis in mouse and rat models of Alzheimer's disease and aging, given in the diet. P21 (P021) is a neurotrophic peptide derived from CNTF (Ciliary Neurotrophic Factor). Research shows enhancement of neurogenesis and synaptic plasticity. Studies demonstrate cognitive improvement potential, particularly for memory and learning processes. ### Benefits Neurogenesis and BDNF elevation in rodent models; no human data ### Dosing reference - Research dose: Vendor/community range 250 to 1000 mcg daily; no published human dose. - Range: 250 to 1000 mcg, 1x daily All chronic rodent studies gave P021 in the diet (60 nmol per g of feed), not by injection (Kazim 2014; Baazaoui 2017). No human pharmacokinetic, dose or safety data exist. Community protocols are subcutaneous. ### Mechanism Proposed neurotrophic action. P021 was built from CNTF residues 148 to 151 with an adamantylated glycine added (Li et al., 2010). In mice, adamantane-modified CNTF peptides promoted neurogenesis and synaptic plasticity, and chronic oral dosing had disease-modifying effects in a triple transgenic Alzheimer's model (Kazim et al., 2014). It prevented dendritic and synaptic deficits (Baazaoui and Iqbal, 2017) and lowered cerebrospinal fluid tau in aged rats (Khatoon et al., 2015). No receptor target has been identified. ### Evidence Preclinical: animal or in vitro data only - Adamantane-modified CNTF peptides improved learning and memory and promoted neurogenesis and synaptic plasticity in mice (Li et al., 2010) - Chronic oral treatment had disease-modifying effects in triple transgenic Alzheimer's mice (Kazim et al., 2014) - Treatment rescued cognitive aging in aged rats (Bolognin et al., 2014) - Early treatment prevented developmental delay and Alzheimer-like memory deficits in Ts65Dn Down syndrome mice (Kazim et al., 2017) - P021 was tested in cell and mouse models of CDKL5 deficiency disorder by an independent group (Mottolese et al., 2024) - Human-trial status: none. All animal dosing was dietary or oral, with no injectable study, and nearly all work comes from one group (Iqbal laboratory) ### References - [Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. Li B, Wanka L, Blanchard J, et al., FEBS Letters, 2010](https://doi.org/10.1016/j.febslet.2010.06.025) - [Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Kazim SF, Blanchard J, Dai CL, et al., Neurobiology of Disease, 2014](https://doi.org/10.1016/j.nbd.2014.07.001) - [Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Bolognin S, Buffelli M, Puoliväli J, et al., Neurobiology of Aging, 2014](https://doi.org/10.1016/j.neurobiolaging.2014.02.017) - [Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Baazaoui N, Iqbal K, Alzheimer's Research & Therapy, 2017](https://doi.org/10.1186/s13195-017-0273-7) - [Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer's-like memory deficits in the Ts65Dn mouse model of Down syndrome. Kazim SF, Blanchard J, Bianchi R, et al., Scientific Reports, 2017](https://doi.org/10.1038/srep45561) - [Elevated Tau Level in Aged Rat Cerebrospinal Fluid Reduced by Treatment with a Neurotrophic Compound. Khatoon S, Chalbot S, Bolognin S, et al., Journal of Alzheimer's Disease, 2015](https://doi.org/10.3233/JAD-142799) - [Prenatal to early postnatal neurotrophic treatment prevents Alzheimer-like behavior and pathology in mice. Wei W, Wang Y, Liu Y, et al., Alzheimer's Research & Therapy, 2020](https://doi.org/10.1186/s13195-020-00666-7) - [Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder. Mottolese N, Loi M, Trazzi S, et al., Journal of Neurodevelopmental Disorders, 2024](https://doi.org/10.1186/s11689-024-09583-4) ### Side effects No human safety data; effects unknown beyond animal studies, where rodent work reported no overt toxicity. Human pharmacokinetics, dosing, and long-term neurological effects are entirely uncharacterized. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not reported in the sources reviewed; no human data - Bioavailability: Orally active in mice when given in the diet (Kazim et al., 2014); not measured in humans or by injection - Molecular weight: 578.7 Da - Sequence: Ac-DGGL-[adamantylglycine]-NH2 ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Pal-AHK URL: https://peptidelabs.app/peptides/pal-ahk/ Also known as: Palmitoyl Tripeptide-52 Amide, Palmitoyl Tripeptide-52, Pal-AHK-NH2 Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Palmitoylated, amidated tripeptide Ala-His-Lys, known only from the EU cosmetic ingredient register (Palmitoyl Tripeptide-52 Amide); no published study of this compound exists. Pal-AHK is listed in the EU CosIng register as Palmitoyl Tripeptide-52 Amide: a palmitoyl chain on Ala-His-Lys with a C-terminal amide. No paper in PubMed tests it, and PubChem has no entry. The old text's claims of better penetration, follicle delivery and prolonged activity had no source. The only related data are on the copper complex AHK-Cu, tested on human hair follicles ex vivo (Pyo 2007) and described in a 2026 review as ex vivo only (Fan 2026). Those results belong to the AHK-Cu entry and do not transfer to this compound. No human trial exists. ### Benefits None published for Pal-AHK. The copper complex AHK-Cu has ex vivo human hair follicle data only (see AHK-Cu entry) ### Dosing reference - Research dose: Topical Topical cosmetic ingredient. No published use concentration or dose, and no study of this compound in any model. ### Mechanism Unknown; no study has tested Pal-AHK. The old text borrowed GHK-Cu claims (VEGF, KGF, anagen prolongation) without a source. The palmitoyl chain raises lipophilicity by design, but no skin penetration study of this compound has been published. For the copper complex, see the AHK-Cu entry (Pyo 2007). ### Evidence Anecdotal: no peer-reviewed data - No published study of Pal-AHK in any model; identity rests on the EU CosIng entry Palmitoyl Tripeptide-52 Amide - A vitamin C-linker conjugate of AHK, a different molecule, stimulated BMP-2-induced osteogenic differentiation of mouse C2C12 myoblasts (Jung et al., 2018) - Human-trial status: none for Pal-AHK. Only the copper complex AHK-Cu has hair data, on human follicles ex vivo, with a non-significant change in apoptosis (Pyo et al., 2007; Fan et al., 2026); see the AHK-Cu entry ### References - [The effect of tripeptide-copper complex on human hair growth in vitro. Pyo HK, Yoo HG, Won CH, Lee SH, et al., Archives of Pharmacal Research, 2007](https://doi.org/10.1007/BF02978833) - [Overview of Short Peptides for Hair Loss. Fan C, Chen Y, Huang Q, Ou WY, et al., Biomedicines, 2026](https://doi.org/10.3390/biomedicines14040864) - [Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells. Jung JI, Park KY, Lee Y, Park M, et al., Differentiation, 2018](https://doi.org/10.1016/j.diff.2018.03.001) ### Side effects No published safety data for this compound in any species. Commonly reported (anecdotal): irritation, redness or stinging with topical peptide products. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published data in any species - Bioavailability: Not measured; no skin penetration study of this compound has been published - Molecular weight: 591.84 Da - Sequence: [Palmitoyl]-AHK-[NH2] (Ala-His-Lys amide) ### Categories - [Hair Growth](https://peptidelabs.app/peptides/category/hair-growth/) - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) ## Pal-GHK (Palmitoyl Tripeptide-1) URL: https://peptidelabs.app/peptides/pal-ghk-palmitoyl-tripeptide-1/ Also known as: Palmitoyl Tripeptide-1, Biopeptide CL, Pal-GHK, Palmitoyl Oligopeptide (former INCI name) Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Palmitoyl tripeptide-1 (Pal-GHK), a lipidated GHK sold mainly in the Matrixyl 3000 blend; found in human stratum corneum after topical use, with no published single-ingredient efficacy trial. Pal-GHK is GHK with an N-terminal palmitoyl chain. It was sold for years as 'palmitoyl oligopeptide', a name that covered two molecules until it was renamed palmitoyl tripeptide-1 in 2013 (Resende et al., 2021). It is usually supplied with palmitoyl tetrapeptide-7 as Matrixyl 3000. Sederma authors reported that this blend improved dermal matrix structure versus placebo (Mondon et al., 2015). In three volunteers it was detected through every layer of the stratum corneum, between rather than inside cells (Trzaska et al., 2026). The CIR panel found it safe in cosmetics at typical use below 10 ppm (Johnson et al., 2018). No peer-reviewed study tests Pal-GHK alone for efficacy. ### Benefits Dermal matrix and junction changes vs placebo when blended with palmitoyl tetrapeptide-7 (supplier-run human study), stratum corneum uptake (human in vivo, n=3) ### Dosing reference - Research dose: Topical, typically under 10 ppm in finished products (CIR 2018); no trial-derived concentration for the peptide alone. No oral or injectable dose exists. Topical only. CIR reports typical use under 10 ppm. Human data come from supplier studies of the Matrixyl 3000 blend with palmitoyl tetrapeptide-7, not the isolated peptide. ### Mechanism Proposed, by analogy to GHK. Supplier literature describes Pal-GHK as a matrikine signal peptide that stimulates collagen and glycosaminoglycans, and a review classes it as a signal peptide (Errante et al., 2020), but no peer-reviewed primary study measures these effects for Pal-GHK itself. The palmitoyl chain is meant to aid skin entry; in human volunteers the peptide stayed in intercellular spaces of the stratum corneum (Trzaska et al., 2026). TGF-beta activation and gene-level tissue repair are claims about GHK or GHK-Cu, not shown for this compound. ### Evidence Preclinical: animal or in vitro data only - Blend with palmitoyl tetrapeptide-7, sold as Matrixyl 3000, thinned the subepidermal low-echogenic band and improved dermal matrix structure vs placebo by in vivo confocal microscopy; Sederma-run (Mondon et al., 2015) - Detected through all stratum corneum layers, intercellularly, in 3 volunteers after a Matrixyl 3000 serum (Trzaska et al., 2026) - CIR panel: safe in cosmetics at present use, typically under 10 ppm, based on negative safety tests (Johnson et al., 2018) - Human-trial status: no published RCT of Pal-GHK alone; human efficacy data are blend studies from the supplier ### References - [Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics. Johnson W, Bergfeld WF, Belsito DV, Hill RA, et al., International Journal of Toxicology, 2018](https://doi.org/10.1177/1091581818807863) - [Evaluation of dermal extracellular matrix and epidermal-dermal junction modifications using matrix-assisted laser desorption/ionization mass spectrometric imaging, in vivo reflectance confocal microscopy, echography, and histology: effect of age and peptide applications. Mondon P, Hillion M, Peschard O, Andre N, et al., Journal of cosmetic dermatology, 2015](https://doi.org/10.1111/jocd.12135) - [Permeation behaviour of cosmetic actives into the human stratum corneum. Trzaska AH, Kotowska AM, Starr NJ, Humphreys AJ, et al., International journal of pharmaceutics, 2026](https://doi.org/10.1016/j.ijpharm.2026.127447) - [Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, et al., Pharmaceuticals (Basel, Switzerland), 2021](https://doi.org/10.3390/ph14080702) - [Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Errante F, Ledwoń P, Latajka R, Rovero P, et al., Frontiers in chemistry, 2020](https://doi.org/10.3389/fchem.2020.572923) ### Side effects CIR reviewed negative safety test data and found no concern at use concentrations under 10 ppm (Johnson et al., 2018). No systemic data exist. Commonly reported (anecdotal): mild irritation or redness. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Topical (3 human volunteers, Matrixyl 3000 serum, 0.5 to 5 h): present in all stratum corneum layers, intercellular; deeper penetration not measured - Molecular weight: 578.75 Da - Sequence: Palmitoyl-Gly-His-Lys ### Stacks with - [Rigin (Palmitoyl Tetrapeptide-7)](https://peptidelabs.app/peptides/rigin-palmitoyl-tetrapeptide-7/) ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Palmitoyl Dipeptide-6 URL: https://peptidelabs.app/peptides/palmitoyl-dipeptide-6/ Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Lipidated cosmetic peptide sold under a name whose exact structure could not be confirmed; no peer-reviewed study of any kind was found. The record name matches no single confirmed molecule. Vendors list 'Palmitoyl Dipeptide-6' with CAS 794590-34-4, which PubChem files as palmitoyl-Lys-Val-diaminobutyrate trifluoroacetate under the name palmitoyl dipeptide-5 diaminohydroxybutyrate; a related ingredient, palmitoyl dipeptide-6 diaminohydroxybutyrate, appears on cosmetic ingredient lists. The old record gave Pal-Val-Leu, which matches none of these. No peer-reviewed study of any of these molecules was found in PubMed, so every functional claim rests on supplier literature. ### Benefits Supplier-reported firmness effects only; no peer-reviewed data in any model ### Dosing reference - Research dose: Topical by supplier framing; no published concentration or study. Topical cosmetic ingredient. No peer-reviewed study in any model; supplier data only. ### Mechanism Unknown. Supplier material describes retinoid-like or matrix-stimulating activity, but no peer-reviewed study of this ingredient exists, and the molecule itself is ambiguous. Claims of collagen, elastin and fibronectin upregulation, matrix crosslinking and MMP inhibition have no published source. ### Evidence Anecdotal: no peer-reviewed data - No peer-reviewed study of palmitoyl dipeptide-6 in cells, animals or humans was found in PubMed - Human-trial status: none; all claims come from supplier literature, and the molecule's structure could not be confirmed ### Side effects No safety data in any species. Commonly reported (anecdotal): mild irritation or redness. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Pancragen URL: https://peptidelabs.app/peptides/pancragen/ Also known as: KEDW-NH2, Lys-Glu-Asp-Trp-NH2 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide (KEDW-NH2) for pancreas; improved glucose tolerance in old rhesus monkeys and diabetic rats, plus one small human study against untreated controls. Pancragen is a synthetic tetrapeptide (KEDW, Lys-Glu-Asp-Trp), printed with a C-terminal amide in two of the developer's papers (Khavinson 2007; Khavinson 2022). Oral dosing lowered blood glucose in rats with streptozotocin diabetes (Khavinson 2007). In old female rhesus monkeys, 50 mcg per animal daily intramuscularly for 10 days sped glucose clearance and normalized insulin and C-peptide responses, partly lasting 3 weeks (Goncharova 2014). In pancreatic cell cultures it raised Pdx1, Pax6, Pax4, Foxa2 and Nkx2.2 (Khavinson 2013). In 33 older people with type 2 diabetes compared with untreated patients, fasting glucose, insulin and insulin resistance fell (Korkushko 2011); the abstract reports neither randomization nor dose. ### Benefits Better glucose tolerance and insulin dynamics (old rhesus monkeys), lower blood glucose in streptozotocin diabetes (rat, oral), pancreatic differentiation markers (in vitro), lower fasting glucose and insulin resistance (small human study, randomization not reported) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose. Old monkeys received 50 mcg per animal daily intramuscularly - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection; vial size (20 mg) is not a dose. Old rhesus monkeys received 50 mcg per animal per day intramuscularly for 10 days (Goncharova 2014). Rats received it orally and intramuscularly (Khavinson 2007). No controlled human glycemic data exist. ### Mechanism Proposed. In young and aged human pancreatic cell cultures it raised transcription factors for acinar (Pdx1, Ptf1a) and islet cell differentiation (Pdx1, Pax6, Pax4, Foxa2, Nkx2.2) (Khavinson 2013), and CXCL12 and Hoxa3 in aged cultures (Khavinson 2012). In diabetic rats intramuscular dosing normalized mesenteric capillary adhesion without changing permeability (Khavinson 2007). How these changes lower glucose is not established, and direct effects on insulin secretion have not been measured in isolated islets. ### Evidence Preclinical: animal or in vitro data only - Oral dosing lowered blood glucose in rats with streptozotocin diabetes; intramuscular dosing normalized capillary adhesion (Khavinson et al., 2007) - At 50 mcg per animal daily intramuscularly for 10 days, sped glucose clearance and normalized insulin and C-peptide in old rhesus monkeys (Goncharova et al., 2014) - Raised acinar and islet differentiation factors (Pdx1, Ptf1a, Pax6, Pax4, Foxa2, Nkx2.2) in pancreatic cell cultures (Khavinson et al., 2013) - Raised CXCL12 and Hoxa3 in aged human pancreatic cell cultures (Khavinson et al., 2012) - Human-trial status: one small study (33 older adults with type 2 diabetes against untreated controls; randomization and dose not reported in the abstract) found lower fasting glucose and insulin resistance (Korkushko et al., 2011); no randomized trial ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Effect of pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus. Khavinson VKh, Gavrisheva NA, Malinin VV, Chefu SG, et al., Bulletin of Experimental Biology and Medicine, 2007](https://doi.org/10.1007/s10517-007-0377-3) - [Effects of pancragen on the differentiation of pancreatic cells during their ageing. Khavinson VKh, Durnova AO, Polyakova VO, Tolibova GH, et al., Bulletin of Experimental Biology and Medicine, 2013](https://doi.org/10.1007/s10517-013-1987-6) - [Prospects of using pancragen for correction of metabolic disorders in elderly people. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA, et al., Bulletin of Experimental Biology and Medicine, 2011](https://doi.org/10.1007/s10517-011-1354-4) - [Impact of tetrapeptide pancragen on endocrine function of the pancreas in old monkeys (in Russian). Goncharova ND, Ivanova LG, Oganian TÉ, Vengerin AA, et al., Advances in Gerontology (Uspekhi Gerontologii), 2014](https://pubmed.ncbi.nlm.nih.gov/25946840/) - [Peptides tissue-specifically stimulate cell differentiation during their aging. Khavinson VKh, Linkova NS, Polyakova VO, Kheifets OV, et al., Bulletin of Experimental Biology and Medicine, 2012](https://doi.org/10.1007/s10517-012-1664-1) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. It lowered blood glucose in diabetic rats and in old monkeys, and its interaction with glucose-lowering drugs has not been studied (Goncharova 2014). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured. Active orally in diabetic rats (Khavinson 2007) - Molecular weight: 575.61 Da - Sequence: KEDW[NH2] (Lys-Glu-Asp-Trp-NH2) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## PE-22-28 URL: https://peptidelabs.app/peptides/pe-22-28/ Also known as: Spadin fragment, TREK-1 inhibitor peptide Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Truncated analog of the natriuretic-peptide-derived peptide spadin that blocks the TREK-1 potassium channel; studied in rodents for rapid antidepressant and neurogenic effects. PE-22-28 is a shortened analog of spadin, a peptide derived from the sortilin propeptide. It blocks the TREK-1 two-pore potassium channel, which in rodent studies produces rapid antidepressant-like effects with increased hippocampal neurogenesis and synaptogenesis. No human trials exist; memory and 'nootropic' claims are extrapolation from rodent behavioral assays. ### Benefits Antidepressant-like and anxiolytic effects plus hippocampal neurogenesis in rodent models ### Dosing reference - Research dose: Vendor/community range 100 to 500 mcg daily; no published human dose. - Range: 100 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Dose response is biphasic in mice: mini-spadin at 0.03 mcg/kg activated TREK-1 and was neuroprotective, while 3 mcg/kg inhibited it and was antidepressant (Pietri 2019). Published mouse doses were 3.0 to 4.0 mcg/kg intraperitoneally or 1.0 mg/kg by gavage (Djillani 2017). Community protocols are subcutaneous or intranasal; no human pharmacokinetic or safety data exist. Interaction with serotonergic antidepressants is unstudied. ### Mechanism PE-22-28 is a shortened analog of spadin, a sortilin propeptide fragment that blocks the TREK-1 two-pore potassium channel (Mazella et al., 2010). Deleting TREK-1 in mice produced a depression-resistant phenotype (Heurteaux et al., 2006), the rationale for blocking it. Shortened spadin analogs including PE-22-28 inhibited TREK-1 more strongly than spadin, were more stable in vivo and had antidepressant-like activity in mice (Djillani et al., 2017). The dose response on TREK-1 was biphasic (Pietri et al., 2019). ### Evidence Preclinical: animal or in vitro data only - TREK-1 deletion in mice produced a depression-resistant phenotype (Heurteaux et al., 2006) - Spadin, the parent peptide, blocked TREK-1 and had antidepressant-like effects in rodents (Mazella et al., 2010) - Shortened spadin analogs including PE-22-28 showed better TREK-1 inhibition, in vivo stability and antidepressant-like activity in mice (Djillani et al., 2017) - Sortilin-derived peptides improved stroke recovery and post-stroke depression in mice, with a biphasic dose response on TREK-1 (Pietri et al., 2019) - Human-trial status: none. No human pharmacokinetic, dose or safety data ### References - [Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Heurteaux C, Lucas G, Guy N, et al., Nature Neuroscience, 2006](https://doi.org/10.1038/nn1749) - [Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. Mazella J, Pétrault O, Lucas G, et al., PLoS Biology, 2010](https://doi.org/10.1371/journal.pbio.1000355) - [Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Djillani A, Pietri M, Moreno S, et al., Frontiers in Pharmacology, 2017](https://doi.org/10.3389/fphar.2017.00643) - [First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Pietri M, Djillani A, Mazella J, et al., Neuropharmacology, 2019](https://doi.org/10.1016/j.neuropharm.2019.107715) ### Side effects No human safety data; effects unknown beyond animal studies in rodents. As a TREK-1 potassium channel blocker, its effects on cardiac and neural channels in humans are entirely uncharacterized. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No human data. More stable in vivo than spadin in mice (Djillani et al., 2017); no half-life figure verified in this audit - Bioavailability: Not measured in humans; no bioavailability figure verified in the published sources - Molecular weight: 848 Da - Sequence: 7-amino acid sequence derived from spadin (sortilin propeptide fragment 22-28) ### Stacks with - [Semax](https://peptidelabs.app/peptides/semax/) - [Selank](https://peptidelabs.app/peptides/selank/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## PEG-MGF URL: https://peptidelabs.app/peptides/peg-mgf/ Also known as: Pegylated Mechano Growth Factor, PEG-IGF-1 Ec Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview PEGylated version of mechano growth factor (the IGF-1Ec splice variant), sold as a research chemical; no published pharmacology or human data exist for the PEGylated form. PEG-MGF is a grey-market PEGylated form of the synthetic IGF-1Ec E-domain peptide (MGF, id 54). No pharmacokinetic, efficacy or safety study of the PEGylated form has been published in any species, so the claims of extended half-life and systemic availability are vendor assertions, not measurements. The unmodified peptide it is built from is itself disputed: the original proliferative result (Yang 2002) failed to replicate across two pharmaceutical companies at up to 500 ng/mL (Fornaro 2014), and no endogenous MGF peptide has been isolated from cells, medium, tissue or fluid (Matheny 2010). FDA names Mechano growth factor pegylated (PEG-MGF) in the withdrawn-nomination table of its 503A compounding safety-risk page, stating it has identified no human exposure data for the substance by any route. ### Benefits No published effect of any kind for the PEGylated form. The parent peptide increased myoblast proliferation in vitro (contested; a two-company replication found no effect) and was neuroprotective in gerbil brain ischemia (animal) ### Dosing reference - Research dose: 200 to 500 mcg: vendor and community range, no published human or animal dose for the PEGylated form - Range: 200 to 500 mcg, 2-3x weekly - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg No published human or animal data for the PEGylated form; doses are community convention. IGF-family signaling raises theoretical concerns about hypoglycemia and promotion of existing tumors - avoid with active or suspected malignancy. ### Mechanism Sold as the MGF E-domain peptide conjugated to polyethylene glycol. The proposed mechanism is the parent peptide's: increased myoblast proliferation with delayed differentiation through a receptor other than IGF-1R (Yang 2002). That effect is contested, since a two-company replication found none up to 500 ng/mL (Fornaro 2014), and no endogenous peptide matching MGF has been isolated from any biological source (Matheny 2010). For the PEGylated form specifically, nothing is published: no conjugation chemistry, no site of attachment, no clearance measurement, no activity assay. PEGylation generally slows proteolysis and renal clearance, but whether that holds here, and at what cost to potency, has not been tested. ### Evidence Anecdotal: no peer-reviewed data - No study of PEG-MGF has been published: no pharmacokinetics, no efficacy, no toxicology, in any species - The parent peptide increased myoblast proliferation and inhibited differentiation in vitro, with the effect surviving IGF-1 receptor blockade (Yang and Goldspink, 2002) - A replication across two pharmaceutical companies found no effect of MGF peptide up to 500 ng/mL on human or mouse myoblasts or primary muscle stem cells, and no p-ERK activation in cardiac myocytes (Fornaro et al., 2014) - No analogous peptide product of the IGF-1 gene has been isolated from cultured cells, conditioned medium, animal tissue or biological fluid (Matheny et al., 2010) - Human-trial status: none for the PEGylated form or the parent peptide. FDA states it has identified no human exposure data for PEG-MGF administered by any route ### References - [Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. Yang SY, Goldspink G, FEBS Letters, 2002](https://doi.org/10.1016/s0014-5793(02)02918-6) - [Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells. Fornaro M, Hinken AC, Needle S, et al., American Journal of Physiology. Endocrinology and Metabolism, 2014](https://doi.org/10.1152/ajpendo.00408.2013) - [Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Matheny RW Jr, Nindl BC, Adamo ML, Endocrinology, 2010](https://doi.org/10.1210/en.2009-1217) - [A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. Dluzniewska J, Sarnowska A, Beresewicz M, et al., FASEB Journal, 2005](https://doi.org/10.1096/fj.05-3786fje) - [Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise. Hameed M, Orrell RW, Cobbold M, Goldspink G, Harridge SD, The Journal of Physiology, 2003](https://doi.org/10.1113/jphysiol.2002.032136) ### Side effects No data exist for the PEGylated form in any species, and FDA states it has identified no human exposure data for PEG-MGF by any route. Repeated PEG exposure carries its own uncertainty, including anti-PEG antibody formation. Hypoglycemia is the risk usually cited for IGF-1 family peptides through insulin receptor cross-reactivity, but the E-domain peptide is not IGF-1 and its reported effects were IGF-1R-independent, so that concern is inferred rather than measured. Proliferative signaling makes use with active or suspected malignancy inadvisable. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured for the PEGylated form or for the parent peptide. Both figures in the old value were unsourced - Sequence: YQPPSTNKNTKSQRRKGSTFEERK (24 aa IGF-1Ec E domain) plus an undisclosed PEG conjugate ### Stacks with - [IGF-1 LR3](https://peptidelabs.app/peptides/igf-1-lr3/) - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) - [Muscle Growth](https://peptidelabs.app/peptides/category/muscle-growth/) ## Pentapeptide-18 (Leuphasyl) URL: https://peptidelabs.app/peptides/pentapeptide-18-leuphasyl/ Also known as: Leuphasyl, Pentapeptide-18, Tyr-D-Ala-Gly-Phe-Leu Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Leucine-enkephalin analog pentapeptide (Tyr-D-Ala-Gly-Phe-Leu) sold as Leuphasyl for expression lines; evidence is manufacturer data, one small emulsion study and in vitro work. Pentapeptide-18 is a leucine-enkephalin analog with D-alanine at position 2, marketed by Lipotec as Leuphasyl. The efficacy figures in circulation, including synergy with acetyl hexapeptide-8, come from manufacturer documents rather than peer-reviewed trials (Errante et al., 2020). A small Romanian study tested 0.5, 1 and 2% emulsions over the brow and periorbital muscles to choose a concentration; it was not placebo-controlled (Dragomirescu et al., 2014). Recent independent work is computational and in vitro (Akhan et al., 2026). The comparison to injected botulinum toxin is marketing, not a measured equivalence. ### Benefits Expression-line reduction (manufacturer data, not peer reviewed), no keratinocyte cytotoxicity up to 1 mg/mL (in vitro) ### Dosing reference - Research dose: Topical, 0.5 to 2% emulsions in the one published human study; whether this is pure peptide or supplier solution is not stated in the abstract. Topical only. The one published study compared 0.5, 1 and 2% emulsions applied over the facial muscles rather than on the wrinkles. Other human data are manufacturer-run, often with acetyl hexapeptide-8. ### Mechanism Proposed. The manufacturer describes binding to enkephalin receptors on nerve terminals that lowers acetylcholine release at the neuromuscular junction, independent of and additive to the SNARE mechanism of acetyl hexapeptide-8 (Errante et al., 2020; Dragomirescu et al., 2014). No peer-reviewed study has measured receptor binding, acetylcholine release or muscle activity after topical use. Docking studies predict binding to MMP-13 and signalling proteins, which is untested in cells (Akhan et al., 2026). ### Evidence Preclinical: animal or in vitro data only - Emulsions at 0.5, 1 and 2% applied over the corrugator and orbicularis muscles to find an optimal concentration; uncontrolled, effect sizes not given in the abstract (Dragomirescu et al., 2014) - Manufacturer data report expression-line reduction and synergy with acetyl hexapeptide-8; a review cites them as company documents, not peer-reviewed trials (Errante et al., 2020) - No cytotoxicity in HaCaT keratinocytes up to 1 mg/mL; docking predicts MMP-13 binding (Akhan et al., 2026) - Analogs with a terminal D-tyrosine reduced melanin in MNT-1 cells and a 3D skin model; the parent was the comparator (Park et al., 2020) - Human-trial status: no published randomized or placebo-controlled human trial; efficacy figures are manufacturer data ### References - [The Efficiency and Safety of Leuphasyl—A Botox-Like Peptide. Dragomirescu A, Andoni M, Ionescu D, Andrei F, Cosmetics, 2014](https://doi.org/10.3390/cosmetics1020075) - [Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Errante F, Ledwoń P, Latajka R, Rovero P, et al., Frontiers in chemistry, 2020](https://doi.org/10.3389/fchem.2020.572923) - [Integrative In Silico and In Vitro Evaluation of Vialox and Leuphasyl Pentapeptides for Antiaging Applications. Akhan D, Bicak B, Kurtur OB, Budama-Kilinc Y, et al., Chemistry & biodiversity, 2026](https://doi.org/10.1002/cbdv.202502546) - [Pentapeptide-18 as an anti-aging candidate: Spectroscopic characterization and molecular interaction analysis. Akhan D, Bicak B, Akalin E, Gunduz SK, Computational biology and chemistry, 2026](https://doi.org/10.1016/j.compbiolchem.2026.108952) - [D-tyrosine adds an anti-melanogenic effect to cosmetic peptides. Park J, Jung H, Jang B, Song HK, et al., Scientific reports, 2020](https://doi.org/10.1038/s41598-019-57159-3) ### Side effects No cytotoxicity in keratinocytes up to 1 mg/mL (Akhan et al., 2026); the small emulsion study assessed tolerability but its abstract gives no results (Dragomirescu et al., 2014). The sequence is an opioid-peptide analog; systemic effects have not been studied. Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured; in silico ADME only (Akhan et al., 2026). Penetration to muscle is unproven - Molecular weight: 569.66 Da - Sequence: Tyr-[D-Ala]-Gly-Phe-Leu ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## PHDP5 URL: https://peptidelabs.app/peptides/phdp5/ Also known as: PHDP5-CPP (cell-penetrating conjugate), dynamin 1 PH domain peptide 5 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Dodecapeptide from the dynamin 1 pleckstrin homology domain that blocks microtubule-dynamin binding; intranasal dosing rescued memory in Alzheimer-model mice. No human data. PHDP5 is a synthetic twelve-residue peptide taken from the pleckstrin homology domain of dynamin 1, the protein that pinches off synaptic vesicles. In an Alzheimer synapse model, excess presynaptic tau assembles microtubules that trap dynamin, and endocytosis fails; PHDP5 inhibits that trapping and restores vesicle recycling (Hori et al., 2022). Given intranasally as a cell-penetrating conjugate, it reached the hippocampus and brought water-maze performance in two Alzheimer mouse lines close to wild-type controls (Chang et al., 2024). The work comes from a single group, there is no pharmacokinetic or safety study in any species, and nothing has been tested in people. ### Benefits Rescued vesicle endocytosis and synaptic transmission in a tau synapse model (mouse), improved water-maze learning in two Alzheimer mouse lines; no human data ### Dosing reference - Research dose: 100 to 500 mcg daily (vendor/community range, no published human dose) - Range: 100 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Emerging research peptide. Doses in circulation are community convention with no pharmacokinetic basis; no human safety data. ### Mechanism PHDP5 is a synthetic dodecapeptide copying residues 560 to 571 of the pleckstrin homology domain of dynamin 1. In the calyx of Held synapse model, loading wild-type human tau into presynaptic terminals assembled microtubules and sequestered free dynamin, impairing vesicle endocytosis and causing activity-dependent rundown of transmission; PHDP5 blocked the microtubule-dynamin interaction and rescued both (Hori et al., 2022). It was identified by screening 22 peptides from the domain, and it reduced dynamin recovered with microtubules in a binding assay. For animal work it was made cell-permeable by fusing a cell-penetrating peptide and a FITC tag, then given intranasally (Chang et al., 2024). It is not a neurogenic peptide and no neural stem cell effect has been reported. ### Evidence Preclinical: animal or in vitro data only - Screening 22 peptides from the dynamin 1 PH domain identified PHDP5 as the one that blocks microtubule-dynamin binding (Hori et al., 2022) - Co-loading PHDP5 with wild-type human tau in mouse calyx of Held terminals rescued vesicle endocytosis and prevented activity-dependent rundown of transmission; a scrambled peptide did not (Hori et al., 2022) - Intranasal FITC-PHDP5 with a cell-penetrating peptide reached the hippocampus in Tau609 transgenic and 3xTg-AD mice (Chang et al., 2024) - In the Morris water maze, treated Alzheimer-model mice performed close to saline-infused wild-type controls, while the scrambled construct gave no improvement (Chang et al., 2024) - Human-trial status: none. Two primary papers exist, both from one group, and there are no pharmacokinetic, dose-ranging or toxicology data in any species ### References - [Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer's disease synapse model. Hori T, Eguchi K, Wang HY, et al., eLife, 2022](https://doi.org/10.7554/eLife.73542) - [The microtubule-dynamin binding inhibitor peptide PHDP5 rescues spatial learning and memory deficits in Alzheimer's disease model mice. Chang CJ, Taoufiq Z, Yamada H, et al., Brain Research, 2024](https://doi.org/10.1016/j.brainres.2024.148987) - [Therapeutic potential of small peptides in Alzheimer's disease: Advances in memory restoration and targeted delivery systems. Verma P, Khatun R, Jew KA, et al., Neuropeptides, 2025](https://doi.org/10.1016/j.npep.2025.102559) ### Side effects No human safety data; effects unknown beyond animal studies in mice. Human pharmacokinetics, dosing, and toxicity are entirely uncharacterized, and the compound is too recent for any meaningful safety literature to exist. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not established; no pharmacokinetic study exists in any species - Bioavailability: Intranasal delivery of a cell-penetrating-peptide conjugate put FITC-labelled peptide in mouse hippocampus (Chang et al., 2024); no subcutaneous data and no quantified bioavailability by any route - Molecular weight: 1467.74 Da - Sequence: EKKYMLSVDNLK (dynamin 1 pleckstrin homology domain, residues 560-571; animal studies used a cell-penetrating-peptide conjugate) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Pinealon URL: https://peptidelabs.app/peptides/pinealon/ Also known as: EDR peptide, Glu-Asp-Arg Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tripeptide (EDR) from the brain drug Cortexin; protected neurons from oxidative stress in vitro and in rats, and preserved dendritic spines in Alzheimer model mice. Pinealon (EDR, Glu-Asp-Arg) is a synthetic tripeptide that the developer describes as isolated from Cortexin, a brain cortex peptide drug (Khavinson 2020). It is not a pineal peptide; the pineal preparations in the family are Epitalon and Epithalamin. It cut ROS and necrotic death in rat cerebellar neurons and PC12 cells under oxidative stress (Khavinson 2011), improved learning in offspring of rats with prenatal hyperhomocysteinemia (Arutjunyan 2012), and at 400 mcg/kg intraperitoneally daily raised hippocampal spine density 11% in Alzheimer model mice (Khavinson 2021). Human reports are uncontrolled: 32 patients with organic brain syndrome (Meshchaninov 2015) and 72 with brain injury, cited only in a review. ### Benefits Lower ROS and necrotic death in neurons under oxidative stress (in vitro), better learning in offspring of hyperhomocysteinemic rats (rodent), dendritic spine preservation in Alzheimer model mice (rodent), small uncontrolled human reports (human, low quality) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose. Mice received 400 mcg/kg intraperitoneally - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. Mice received 400 mcg/kg intraperitoneally once daily for 2 months (Khavinson 2021). Human reports used oral dosing; doses are not given in the indexed abstracts (Khavinson 2020). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed. In cerebellar granule cells, neutrophils and PC12 cells it limited ROS accumulation dose-dependently, delayed ERK1/2 activation and altered the cell cycle; because cell-cycle effects continued above the doses that saturated ROS control, the authors propose a direct genomic action (Khavinson 2011). Docking places EDR binding sites in promoters of CASP3, GAP43, APOE, SOD2, PPARA and PPARG (Khavinson 2021). The developer's review links it to MAPK/ERK, caspase-3, p53, SOD2 and GPX1 (Khavinson 2020). Melatonin and circadian effects in the old text have no published source. ### Evidence Preclinical: animal or in vitro data only - Dose-dependently limited ROS and necrotic death in cerebellar neurons, neutrophils and PC12 cells under oxidative stress (Khavinson et al., 2011) - Given to pregnant rats with methionine-induced hyperhomocysteinemia, improved offspring learning and neuron resistance to oxidative stress (Arutjunyan et al., 2012) - At 200 ng/mL, raised mushroom spines 71% in hippocampal neurons exposed to amyloid beta (Kraskovskaya et al., 2017) - At 400 mcg/kg intraperitoneally daily for 2 months, raised CA1 spine density 11% in 5xFAD-M mice; LTP rescue was not significant (Khavinson et al., 2021) - Human-trial status: no randomized trial. An uncontrolled study of 32 patients with organic brain syndrome reported biological-age changes and prooxidant activity (Meshchaninov et al., 2015) ### References - [Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. Khavinson V, Ribakova Y, Kulebiakin K, Vladychenskaya E, et al., Rejuvenation Research, 2011](https://doi.org/10.1089/rej.2011.1172) - [Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. Arutjunyan A, Kozina L, Stvolinskiy S, Bulygina Y, et al., International Journal of Clinical and Experimental Medicine, 2012](https://pubmed.ncbi.nlm.nih.gov/22567179/) - [Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease. Kraskovskaya NA, Kukanova EO, Lin'kova NS, Popugaeva EA, et al., Bulletin of Experimental Biology and Medicine, 2017](https://doi.org/10.1007/s10517-017-3847-2) - [Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease. Khavinson V, Ilina A, Kraskovskaya N, Linkova N, et al., Pharmaceuticals, 2021](https://doi.org/10.3390/ph14060515) - [EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease. Khavinson V, Linkova N, Kozhevnikova E, Trofimova S, Molecules, 2020](https://doi.org/10.3390/molecules26010159) - [EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION (in Russian). Meshchaninov VN, Tkachenko EL, Zharkov SV, Gavrilov IV, et al., Advances in Gerontology (Uspekhi Gerontologii), 2015](https://pubmed.ncbi.nlm.nih.gov/26390612/) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. An uncontrolled human study reported prooxidant activity by chemiluminescence and fewer circulating CD34+ cells (Meshchaninov 2015). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species; oral use reported in uncontrolled human studies (Khavinson 2020) - Molecular weight: 418.4 Da - Sequence: EDR (Glu-Asp-Arg) ### Stacks with - [Vesugen](https://peptidelabs.app/peptides/vesugen/) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) ## PNC-27 URL: https://peptidelabs.app/peptides/pnc-27/ Also known as: PNC27, p53(12-26)-penetratin, p53(15)Ant Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic 32-residue peptide joining p53 residues 12-26 to the penetratin cell-penetrating sequence; it lysed cancer cells but spared normal cells in vitro and prolonged survival in leukemic mice. PNC-27 was designed by the Pincus and Michl group at SUNY Downstate from conformational analysis of the HDM-2 binding domain of p53. It joins p53 residues 12 to 26 to penetratin, a 17-residue sequence from Antennapedia that carries peptides across membranes. The first paper found it killed many human cancer lines, including p53-null ones, but not normal cells or cord-blood stem cells (Kanovsky 2001). Later work found HDM-2 in the outer membrane of cancer cells and proposed that PNC-27 binds it and forms pores, killing by necrosis within hours rather than by apoptosis (Sarafraz-Yazdi 2010). In vivo data are mouse models of acute myeloid leukemia from an independent group (Wang 2020) and of ovarian cancer with paclitaxel. No human trial has been published or registered. ### Benefits Selective killing of cancer cell lines by membrane lysis (in vitro); reduced leukemia burden and longer survival in AML mouse models; added to paclitaxel's effect in a mouse ovarian cancer model. No human data ### Dosing reference - Research dose: No published human dose. Mouse studies used 40 to 100 mg/kg intraperitoneally daily - Common vial sizes: 5 mg No human dose, route or pharmacokinetic study has been published. In AML mouse models PNC-27 was given at 40 mg/kg intraperitoneally daily for 2 to 3 weeks, and at 100 mg/kg daily for 2 weeks in healthy and leukemic mice (Wang et al., 2020). In cell culture it killed cancer cells within hours. Vendors sell 5 mg vials; that is a vial size, not a dose. ### Mechanism Proposed by the developers' group. The p53 12-26 segment of PNC-27 takes the alpha-helical shape it has when bound to HDM-2. HDM-2 was found in the plasma membrane of many cancer cell lines but not of untransformed lines, PNC-27 colocalized with it, and forcing membrane HDM-2 into resistant MCF-10-2A cells made them susceptible (Sarafraz-Yazdi 2010). The intact peptide, not fragments, sat in cancer cell membranes during lysis (Sookraj 2010), and immuno-electron microscopy showed PNC-27 and HDM-2 in about 1:1 ratios lining ring-shaped pores (Sarafraz-Yazdi 2022). Killing does not depend on p53 status. An independent AML study proposed that PNC-27 strengthens the link between membrane HDM2 and E-cadherin, leading to E-cadherin degradation and membrane damage (Wang 2020). ### Evidence Preclinical: animal or in vitro data only - Peptides from p53 residues 12-26 fused to penetratin killed human cancer cell lines, including p53-null lines, but did not affect normal cells or cord-blood stem cells, and did not induce Bax or p21 (Kanovsky et al., 2001) - The same p53(12-26)-penetratin peptide caused rapid necrosis-like death in three breast cancer lines with minimal toxicity to nonmalignant breast epithelial cells (Do et al., 2003) - HDM-2 was found in the membranes of cancer cells but not untransformed lines; PNC-27 colocalized with it, and adding membrane HDM-2 to resistant cells made them susceptible (Sarafraz-Yazdi et al., 2010) - In human and mouse AML models, 40 mg/kg daily intraperitoneally reduced leukemia burden and leukemia stem cells and lengthened median survival (54 vs 41 days with a control peptide) while sparing normal hematopoietic stem cells (Wang et al., 2020) - Added to weekly paclitaxel, PNC-27 reduced tumor growth in a mouse ovarian cancer model, and paclitaxel-surviving cells expressed more membrane MDM-2 (Alagkiozidis et al., 2017) - Human-trial status: none published, and none registered on ClinicalTrials.gov. Nearly all work comes from the developers' group, whose members hold patents on PNC-27; the AML study was independent but used peptide supplied by Oncolyze. The shorter analog PNC-28 blocked pancreatic tumor growth in mice (Michl et al., 2006) ### References - [Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells. Kanovsky M, Raffo A, Drew L, Rosal R, et al., Proceedings of the National Academy of Sciences of the USA, 2001](https://doi.org/10.1073/pnas.211280698) - [Preferential induction of necrosis in human breast cancer cells by a p53 peptide derived from the MDM2 binding site. Do TN, Rosal RV, Drew L, Raffo AJ, et al., Oncogene, 2003](https://doi.org/10.1038/sj.onc.1206258) - [Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes. Sarafraz-Yazdi E, Bowne WB, Adler V, Sookraj KA, et al., Proceedings of the National Academy of Sciences of the USA, 2010](https://doi.org/10.1073/pnas.0909364107) - [The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Sookraj KA, Bowne WB, Adler V, Sarafraz-Yazdi E, Michl J, Pincus MR, Cancer Chemotherapy and Pharmacology, 2010](https://doi.org/10.1007/s00280-009-1166-7) - [PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis. Sarafraz-Yazdi E, Mumin S, Cheung D, Fridman D, et al., Biomedicines, 2022](https://doi.org/10.3390/biomedicines10050945) - [Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia. Wang H, Zhao D, Nguyen LX, Wu H, et al., Leukemia, 2020](https://doi.org/10.1038/s41375-019-0522-9) - [Synergy between Paclitaxel and Anti-Cancer Peptide PNC-27 in the Treatment of Ovarian Cancer. Alagkiozidis I, Gorelick C, Shah T, Chen YA, et al., Annals of Clinical and Laboratory Science, 2017](https://pubmed.ncbi.nlm.nih.gov/28667027/) - [PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo. Michl J, Scharf B, Schmidt A, Huynh C, et al., International Journal of Cancer, 2006](https://doi.org/10.1002/ijc.22029) ### Side effects No human safety data exist, and no formal toxicology study has been published. In mice, 100 mg/kg intraperitoneally daily for 2 weeks did not impair normal hematopoietic stem cell function (Wang et al., 2020). In vitro it spared several untransformed cell lines, but that selectivity depends on membrane HDM-2 levels and has been tested mainly by the developers. As a pore-forming peptide, damage to normal cells that carry membrane HDM-2 is a theoretical risk that has not been studied. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured: no published pharmacokinetic study in any species. In cell culture the intact peptide persisted in cancer cell membranes but was degraded on untransformed cells (Sookraj et al., 2010) - Bioavailability: Not measured. Mouse efficacy studies gave it intraperitoneally (Wang et al., 2020) - Molecular weight: 4031.8 Da - Sequence: PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG [p53 12-26 + penetratin, free C-terminal acid] ### Categories - [Immune](https://peptidelabs.app/peptides/category/immune/) ## Prostamax URL: https://peptidelabs.app/peptides/prostamax/ Also known as: Prostomax, KEDP, Lys-Glu-Asp-Pro Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide (KEDP) assigned to prostate; published work is limited to chromatin effects in lymphocytes from elderly donors and one rat explant study. Prostamax (also Prostomax; KEDP, Lys-Glu-Asp-Pro) is a synthetic tetrapeptide from the St. Petersburg Institute of Bioregulation and Gerontology, listed for regulation of prostate function; the source cited for that label is a European patent (Khavinson 2022). Published work: in lymphocytes from people aged 75 to 88 it activated ribosomal genes and decondensed heterochromatin (Khavinson 2004; Dzhokhadze 2012), it shifted chromatin melting in calorimetry (Meskhi 2004), and at 0.05 ng/mL it stimulated rat prostate explants in organotypic culture (Zakutskii 2006). No animal model of prostate disease and no human trial has been published. ### Benefits Chromatin decondensation in lymphocytes from elderly donors (in vitro), growth of prostate explants (rat tissue culture) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection; vial size (20 mg) is not a dose. No in vivo dose has been published in any species. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed, from in vitro work. In lymphocytes from elderly donors it activated ribosomal genes, decondensed chromosome 1 pericentromeric heterochromatin and released genes silenced by age-related condensation (Khavinson 2004). It raised sister chromatid exchange from 5.9 to 12.0 per cell and Ag-positive nucleolar organizer regions from 0.95 to 2.5 per cell (Dzhokhadze 2012), and partly relaxed 30 nm chromatin fibers by calorimetry (Meskhi 2004). Effects on PSA, DHT metabolism or prostate epithelium in the old text have no published source. ### Evidence Preclinical: animal or in vitro data only - Activated ribosomal genes and decondensed heterochromatin, including chromosome 1 pericentromeric regions, in lymphocytes from people aged 75 to 88 (Khavinson et al., 2004) - Raised sister chromatid exchange (5.9 to 12.0 per cell) and active nucleolar organizer regions in lymphocytes from elderly donors (Dzhokhadze et al., 2012) - Shifted chromatin denaturation endotherms in human lymphocytes by calorimetry (Meskhi et al., 2004) - At 0.05 ng/mL, stimulated rat prostate explants in organotypic culture (Zakutskii et al., 2006) - Human-trial status: no published human study and no animal prostate disease model ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Effects of short peptides on lymphocyte chromatin in senile subjects. Khavinson VKh, Lezhava TA, Malinin VV, Bulletin of Experimental Biology and Medicine, 2004](https://doi.org/10.1023/b:bebm.0000024393.40560.05) - [Deheterochromatinization of the chromatin in old age induced by oligopeptide bioregulator (Lys-Glu-Asp-Pro) (in Russian). Dzhokhadze TA, Buadze TZh, Gaĭozishvili MN, Baratashvili NA, et al., Georgian Medical News, 2012](https://pubmed.ncbi.nlm.nih.gov/23221144/) - [The influence of the peptide bioregulator prostamax on heterochromatin of human lymphocytes in situ (in Russian). Meskhi T, Khachidze D, Barbakadze Sh, Madzhagaladze G, et al., Biofizika, 2004](https://pubmed.ncbi.nlm.nih.gov/15612551/) - [The tissue-specific effect of synthetic peptides-biologic regulators in organotypic tissues culture in young and old rats (in Russian). Zakutskiĭ AN, Chalisova NI, Ryzhak GA, Aniskina AI, et al., Advances in Gerontology (Uspekhi Gerontologii), 2006](https://pubmed.ncbi.nlm.nih.gov/17152728/) ### Side effects No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. It raised sister chromatid exchange in cultured lymphocytes, a genotoxicity marker whose meaning here has not been studied (Dzhokhadze 2012). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species - Molecular weight: 487.5 Da - Sequence: KEDP (Lys-Glu-Asp-Pro) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Protirelin URL: https://peptidelabs.app/peptides/protirelin/ Also known as: TRH, Thyrotropin-releasing hormone, Thyroliberin, TRF, Thyrel TRH, Thypinone Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic thyrotropin-releasing hormone (pGlu-His-Pro-NH2) given IV to trigger pituitary TSH and prolactin release in function testing; the US products (1976, 1978) are discontinued. Protirelin is synthetic thyrotropin-releasing hormone (TRH), the hypothalamic tripeptide that releases TSH and prolactin from the anterior pituitary. The FDA approved it as Thypinone (NDA 017638, 1976) and Thyrel TRH (NDA 018087, 1978) for the TRH stimulation test of pituitary TSH reserve; both are discontinued, and DailyMed lists only bulk protirelin powder. Human use is a single IV bolus, with dose-response work from 25 to 800 mcg (Garbutt 1994). Same molecule as the Thyrotropin TRH entry (id 71). ### Benefits Diagnostic stimulation of TSH and prolactin release (established clinical use) ### Dosing reference - Research dose: 200 to 500 mcg IV (single diagnostic bolus) - Range: 200 to 500 mcg, Diagnostic single dose - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 1 mg Human dosing is a single intravenous bolus for the TSH-stimulation test; published dose-response work used 25 to 800 mcg IV, with 200 to 500 mcg the usual diagnostic dose (Garbutt 1994; Doi 2007). Intrathecal 500 mcg has been used in depression research (Marangell 1997). Effects within minutes of injection include a transient blood pressure change, flushing, nausea, an urge to urinate and an odd taste, and prolactin rises acutely. No repeated-dosing protocol has been established in humans. ### Mechanism TRH is a hypothalamic tripeptide (pGlu-His-Pro-NH2) that reaches the anterior pituitary through the portal circulation and stimulates TSH release from thyrotrophs through the Gq-coupled TRH receptor and phospholipase C signalling; it also releases prolactin (Joseph-Bravo 2015; Gary 2003). TSH in turn drives thyroid hormone output, and thyroid hormone feeds back on hypophysiotropic TRH neurons (Joseph-Bravo 2015). Circulating TRH is degraded quickly, with a plasma half-life near 7 minutes in humans (Iversen 1988). TRH receptors are also expressed in the CNS, and intrathecal dosing produced short-lived mood effects in refractory depression, which is the basis for calling TRH a proposed homeostatic modulator (Marangell 1997; Gary 2003). ### Evidence Clinical: at least one published human trial or an approved drug - Protirelin injection was approved by the FDA as a diagnostic agent for pituitary TSH reserve: Thypinone (NDA 017638, Abbott, 1976) and Thyrel TRH (NDA 018087, Ferring, 1978); both are listed as discontinued - Human intravenous pharmacokinetics: plasma half-life 6.6 ± 1.5 min and clearance 1532 ± 423 mL/min in 14 healthy subjects (Iversen, 1988) - Dose-response study using 25, 100, 500 and 800 mcg IV in depressed patients and matched controls: depressed men had blunted TSH and prolactin responses (Garbutt et al., 1994) - TRH stimulation testing in patients with basal TSH in the normal range (Doi et al., 2007) - Pituitary apoplexy, meaning hemorrhage into an existing pituitary adenoma, is reported after TRH stimulation testing (Wang et al., 2007) - Human-trial status: human use is diagnostic only, no therapeutic indication is approved, and no US product is currently marketed ### References - [Intra- and extravascular turnover of thyrotrophin-releasing hormone in normal man. Iversen E, Journal of Endocrinology, 1988](https://doi.org/10.1677/joe.0.1180511) - [Dose-response studies with protirelin. Garbutt JC, Mayo JP, Little KY, et al., Archives of General Psychiatry, 1994](https://doi.org/10.1001/archpsyc.1994.03950110035006) - [TRH stimulation when basal TSH is within the normal range: is there "sub-biochemical" hypothyroidism?. Doi SA, Issac D, Abalkhail S, et al., Clinical Medicine & Research, 2007](https://doi.org/10.3121/cmr.2007.756) - [Pituitary apoplexy after thyrotropin-releasing hormone stimulation test in a patient with pituitary macroadenoma. Wang HF, Huang CC, Chen YF, et al., Journal of the Chinese Medical Association, 2007](https://doi.org/10.1016/S1726-4901(08)70026-1) - [60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary-thyroid axis. Joseph-Bravo P, Jaimes-Hoy L, Uribe RM, Charli JL, Journal of Endocrinology, 2015](https://doi.org/10.1530/JOE-15-0124) - [The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: implications for TRH-based therapeutics. Gary KA, Sevarino KA, Yarbrough GG, et al., Journal of Pharmacology and Experimental Therapeutics, 2003](https://doi.org/10.1124/jpet.102.044040) - [Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients. Marangell LB, George MS, Callahan AM, et al., Archives of General Psychiatry, 1997](https://doi.org/10.1001/archpsyc.1997.01830150034007) ### Side effects This is a diagnostic agent with acute hemodynamic effects: transient blood pressure change, flushing, nausea, a strong urge to urinate, and an odd taste occur within minutes of injection. Pituitary apoplexy, meaning hemorrhage into an existing pituitary tumor, is a rare but life-threatening reported complication. It acutely raises prolactin and TSH. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: 6.6 ± 1.5 min plasma (human, IV constant infusion, n=14); degradation half-life in serum in vitro 16.8 ± 9.4 min (Iversen 1988) - Bioavailability: IV: plasma clearance 1532 ± 423 mL/min in healthy adults (Iversen 1988). Intrathecal dosing has been used in humans to bypass poor blood-brain-barrier penetration (Marangell 1997). No oral, intranasal or subcutaneous bioavailability figure located. - Molecular weight: 362.38 Da - Sequence: pGlu-His-Pro-NH2 ### Categories - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) ## Proxofim URL: https://peptidelabs.app/peptides/proxofim/ Also known as: Senolytic peptide Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Proprietary FOXO4-DRI-type senolytic peptide sold for research; the parent peptide disrupts FOXO4-p53 binding to kill senescent cells in mice, but this analog itself is unstudied. Proxofim is marketed as a next-generation analog of FOXO4-DRI, a D-retro-inverso peptide that disrupts the FOXO4-p53 interaction so that p53 relocates to the mitochondria and senescent cells undergo apoptosis. The published mouse data (improved renal function, fitness and fur density in aged mice) belong to FOXO4-DRI, not to Proxofim, for which no peer-reviewed pharmacology, efficacy or safety data exist. ### Benefits Senescent-cell clearance, restored fitness, fur density and renal function, all shown for FOXO4-DRI in aged and fast-aging mice at 5 mg/kg on alternate days. No published data of any kind for this compound ### Dosing reference - Research dose: 5 to 20 mg: vendor convention with no published basis for this compound. FOXO4-DRI mouse studies used 5 mg/kg intravenously or intraperitoneally on alternate days - Range: 5000 to 20000 mcg, 1x daily (short cycles) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg No published data for this analog; doses are vendor/community convention extrapolated from mouse FOXO4-DRI studies. A p53-dependent apoptosis inducer with no human safety data - unknown risk to healthy proliferating tissue; use is experimental. ### Mechanism No pharmacology has been published for this compound, so the mechanism is the vendor's claim that it acts like FOXO4-DRI. For that peptide the mechanism is established: senescent cells retain p53 in the nucleus through an interaction with FOXO4, and a competing peptide causes p53 nuclear exclusion and cell-intrinsic apoptosis selectively in senescent cells (Baar 2017), with solution NMR later showing it binds the disordered second transactivation domain of p53 (Bourgeois 2025). Whether Proxofim shares that mechanism cannot be checked, because its sequence and structure are not published. Senolysis is also not uniformly beneficial: clearing senescent pulmonary endothelial cells worsened pulmonary hemodynamics in rodents (Born 2023). ### Evidence Anecdotal: no peer-reviewed data - Reference compound FOXO4-DRI killed senescent human fibroblasts while sparing controls, and in mice 3 doses of 5 mg/kg on alternate days restored fitness, fur density and renal markers in fast-aging and naturally aged animals (Baar et al., 2017) - Reference compound: solution NMR shows the peptide binds the disordered second transactivation domain of p53, with affinity increased by p53 phosphorylation (Bourgeois et al., 2025) - Reference compound in aged mice: apoptosis of senescent Leydig cells, reduced senescence-associated secretion and higher testosterone output (Zhang et al., 2020) - Contrary result for the mechanism: senolytic clearance of pulmonary endothelial cells with FOXO4-DRI or ABT263 raised right ventricular systolic pressure and worsened vessel remodeling in mice and rats (Born et al., 2023) - Human-trial status: nothing is published about Proxofim in any species, its sequence is not disclosed, and no trial of it or of FOXO4-DRI is registered on ClinicalTrials.gov. Every finding above belongs to FOXO4-DRI, catalog id 41 ### References - [Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Baar MP, Brandt RMC, Putavet DA, Klein JDD, et al., Cell, 2017](https://doi.org/10.1016/j.cell.2017.02.031) - [The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Bourgeois B, Spreitzer E, Platero-Rochart D, Paar M, et al., Nature Communications, 2025](https://doi.org/10.1038/s41467-025-60844-9) - [FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Zhang C, Xie Y, Chen H, Lv L, et al., Aging (Albany NY), 2020](https://doi.org/10.18632/aging.102682) - [Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression. Born E, Lipskaia L, Breau M, Houssaini A, et al., Circulation, 2023](https://doi.org/10.1161/CIRCULATIONAHA.122.058794) ### Side effects No human safety data; effects unknown beyond animal studies. The mechanism is induction of p53-dependent apoptosis, so off-target killing of healthy cells is the principal theoretical risk. Any displayed dose is extrapolated from mouse protocols and is not validated in humans. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No pharmacokinetic data exist for this compound, and none have been published for FOXO4-DRI either - Bioavailability: Not measured. No bioavailability or distribution study exists for this compound, and FOXO4-DRI animal dosing was intravenous or intraperitoneal, never subcutaneous ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## PT-141 URL: https://peptidelabs.app/peptides/pt-141/ Also known as: Bremelanotide, Bremelanotide acetate, Vyleesi, PT-141 acetate Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Bremelanotide, a cyclic melanocortin receptor agonist and close analog of melanotan II; approved by the FDA in 2019 as Vyleesi (1.75 mg SC) for acquired HSDD in premenopausal women. The approved product is Vyleesi, a single-dose 1.75 mg autoinjector; vendor PT-141 vials are not that product. Bremelanotide is a cyclic heptapeptide melanocortin agonist developed from melanotan II. Two 24-week phase 3 trials in 1,267 premenopausal women with acquired, generalized HSDD found more desire and less distress than placebo (Kingsberg 2019), and the FDA approved it in 2019 (NDA 210557); it remains marketed. The label excludes men, postmenopausal women and use to enhance sexual performance. Early trials in men with erectile dysfunction, including sildenafil non-responders, were small and development in men did not continue (Rosen 2004; Diamond 2005). ### Benefits Increased sexual desire and reduced distress in premenopausal women with acquired HSDD (two phase 3 RCTs, FDA-labeled), erectile response in men including sildenafil non-responders (small early trials, not an indication) ### Dosing reference - Research dose: 1.75 mg SC per use (Vyleesi label) - Range: 1750 mcg, As needed - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Vyleesi label: 1.75 mg subcutaneously in the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity; no more than one dose within 24 hours; more than 8 doses per month is not recommended; discontinue after 8 weeks if there is no improvement in desire. The phase 3 trials used this dose (Kingsberg 2019); the phase 2b trial also tested 0.75 and 1.25 mg (Clayton 2016). ### Mechanism Bremelanotide is a nonselective melanocortin receptor agonist with potency order MC1R, MC4R, MC3R, MC5R, MC2R; at therapeutic doses binding to MC1R and MC4R is most relevant (Vyleesi label). MC4R-expressing neurons are found throughout the CNS, but the label states that the mechanism by which it improves HSDD in women is unknown. MC1R on melanocytes drives melanin production, which explains the focal hyperpigmentation seen with repeated dosing. A transient rise in blood pressure with a small fall in heart rate follows each dose (Vyleesi label). ### Evidence Clinical: at least one published human trial or an approved drug - Two identical 24-week phase 3 RCTs (RECONNECT) of 1.75 mg as needed in premenopausal women with HSDD improved desire and reduced distress versus placebo (Kingsberg et al., 2019) - The 52-week open-label extension of the phase 3 trials reported continued effect and no new safety signal (Simon et al., 2019) - Phase 2b dose-finding trial in premenopausal women with female sexual dysfunction tested 0.75, 1.25 and 1.75 mg SC (Clayton et al., 2016) - Subcutaneous PT-141 produced erectile responses in healthy men and in men with an inadequate response to sildenafil (Rosen et al., 2004); low-dose intranasal PT-141 with sildenafil enhanced erection (Diamond et al., 2005) - Human-trial status: approved by the FDA in 2019 as Vyleesi (NDA 210557) for acquired, generalized HSDD in premenopausal women and still marketed; not indicated in men or postmenopausal women ### References - [Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Kingsberg SA, Clayton AH, Portman D, et al., Obstetrics & Gynecology, 2019](https://pubmed.ncbi.nlm.nih.gov/31599840/) - [Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Clayton AH, Althof SE, Kingsberg S, et al., Women's Health, 2016](https://doi.org/10.2217/whe-2016-0018) - [Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Simon JA, Kingsberg SA, Portman D, et al., Obstetrics & Gynecology, 2019](https://doi.org/10.1097/AOG.0000000000003514) - [Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Rosen RC, Diamond LE, Earle DC, et al., International Journal of Impotence Research, 2004](https://doi.org/10.1038/sj.ijir.3901200) - [Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response. Diamond LE, Earle DC, Garcia WD, Spana C, Urology, 2005](https://doi.org/10.1016/j.urology.2004.10.060) ### Side effects Vyleesi label, phase 3 (n=627): nausea 40% versus 1.3% on placebo, mostly after the first dose, flushing 20%, injection-site reactions 13%, headache 11%, vomiting 5%; 18% stopped for adverse reactions versus 2% on placebo. Each dose raises blood pressure by up to 6/3 mmHg, peaking 2 to 4 h, with a small fall in heart rate. Focal hyperpigmentation of the face, gums or breasts in 1%, more with daily dosing and darker skin, not always resolved after stopping. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Terminal half-life about 2.7 h (range 1.9 to 4.0 h) after 1.75 mg SC in humans; Tmax about 1 h (Vyleesi label) - Bioavailability: SC absolute bioavailability about 100% (human, Vyleesi label); 21% protein bound; exposure rises less than dose-proportionally from 0.3 to 10 mg - Molecular weight: 1025.18 Da - Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH ### Stacks with - [Melanotan II](https://peptidelabs.app/peptides/melanotan-ii/) ### Categories - [Sexual Health](https://peptidelabs.app/peptides/category/sexual-health/) ## PTD-DBM URL: https://peptidelabs.app/peptides/ptd-dbm/ Also known as: CXXC5-Dvl competing peptide, PTD-DBM-FITC Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Cell-permeable peptide that blocks the CXXC5-Dishevelled interaction to de-repress Wnt/beta-catenin signaling; studied topically in mice for hair regrowth and wound healing. PTD-DBM fuses a protein transduction domain to the Dishevelled-binding motif of CXXC5, a negative regulator of Wnt signaling. By competing CXXC5 away from Dishevelled it restores Wnt/beta-catenin activity in hair follicles. Mouse studies (notably with valproic acid co-treatment) report new hair follicle neogenesis and accelerated wound healing. There is no human trial data. ### Benefits Hair regrowth and wound-induced hair neogenesis (mouse), faster cutaneous wound healing (mouse), studied in a DHT-induced androgenetic alopecia model (mouse) ### Dosing reference - Research dose: Variable Studied only as a topical solution in mice. The developers' papers use concentrations 100-fold apart: 100 microM in wound studies (Lee 2015) and 10 mM in an androgenetic alopecia model (Ryu 2023). The hair regrowth study combined it with valproic acid (Lee 2017). No human dose, trial or safety data. ### Mechanism A polyarginine protein transduction domain (eight arginines) joined by a four-glycine linker to the Dishevelled-binding motif of CXXC5 (residues 284 to 296). CXXC5 binds Dishevelled and negatively regulates Wnt/beta-catenin signalling in skin wound healing (Lee 2015). The peptide competes with CXXC5 for Dishevelled, which in mouse skin restored Wnt/beta-catenin activity, hair regrowth and wound-induced hair neogenesis (Lee 2017; Kim and Garza 2017). CXXC5 also mediates DHT-induced hair loss through prostaglandin D2 in mice (Ryu 2023). The developers later moved to small-molecule CXXC5 inhibitors such as KY19382 (Ryu 2021). DBM means Dishevelled-binding motif, not a DOPA-binding motif. ### Evidence Preclinical: animal or in vitro data only - Topical PTD-DBM at 100 microM accelerated cutaneous wound healing in mice; CXXC5 acts as a negative regulator of healing (Lee et al., 2015) - With valproic acid, topical PTD-DBM stimulated hair regrowth and wound-induced hair neogenesis in mice (Lee et al., 2017) - Topical PTD-DBM at 10 mM was used in a mouse model of DHT-induced androgenetic alopecia (Ryu et al., 2023) - Delivered from an adhesive hydrogel patch as part of a combination drug therapy for regenerative wound healing in mice (Lee et al., 2023) - Human-trial status: none. All studies are in mice from one Yonsei University group with a commercial interest; the group's successors are small molecules such as KY19382 (Ryu et al., 2021) ### References - [The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing. Lee SH, Kim MY, Kim HY, Lee YM, et al., The Journal of Experimental Medicine, 2015](https://doi.org/10.1084/jem.20141601) - [Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. Lee SH, Seo SH, Lee DH, Pi LQ, et al., The Journal of Investigative Dermatology, 2017](https://doi.org/10.1016/j.jid.2017.04.038) - [The Negative Regulator CXXC5: Making WNT Look a Little Less Dishevelled. Kim D, Garza LA, The Journal of Investigative Dermatology, 2017](https://doi.org/10.1016/j.jid.2017.07.826) - [CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD(2). Ryu YC, Park J, Kim YR, Choi S, et al., Cells, 2023](https://doi.org/10.3390/cells12040555) - [Adhesive Hydrogel Patch-Mediated Combination Drug Therapy Induces Regenerative Wound Healing through Reconstruction of Regenerative Microenvironment. Lee SH, An S, Ryu YC, Seo SH, et al., Advanced Healthcare Materials, 2023](https://doi.org/10.1002/adhm.202203094) - [KY19382, a novel activator of Wnt/β-catenin signalling, promotes hair regrowth and hair follicle neogenesis. Ryu YC, Lee DH, Shim J, Park J, et al., British Journal of Pharmacology, 2021](https://doi.org/10.1111/bph.15438) - [Inhibiting the cytosolic function of CXXC5 accelerates diabetic wound healing by enhancing angiogenesis and skin repair. Kim E, Seo SH, Hwang Y, Ryu YC, et al., Experimental & Molecular Medicine, 2023](https://doi.org/10.1038/s12276-023-01064-3) - [Inhibition of CXXC5 function rescues Alzheimer's disease phenotypes by restoring Wnt/β-catenin signaling pathway. Yoon M, Kim H, Shin H, Lee H, et al., Pharmacological Research, 2023](https://doi.org/10.1016/j.phrs.2023.106836) ### Side effects No safety study in any species; the mouse studies were not designed to detect harm. The effect of sustained Wnt/beta-catenin activation on cell proliferation has not been characterized. No human data. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured. Applied topically to mouse skin; the polyarginine domain is there for cell entry (Lee 2017) - Molecular weight: 3210.86 Da - Sequence: RRRRRRRRGGGGRKTGHQICKFRKCK ### Categories - [Hair Growth](https://peptidelabs.app/peptides/category/hair-growth/) - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## Retatrutide URL: https://peptidelabs.app/peptides/retatrutide/ Also known as: LY3437943, Triple G agonist Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Investigational once-weekly agonist of GIP, GLP-1 and glucagon receptors; in the 80-week TRIUMPH-1 phase 3 trial (n=2339), 12 mg gave 25.0% weight loss versus 3.9% with placebo. Retatrutide (LY3437943) is a 39-residue lipidated peptide from Eli Lilly that activates GIP, GLP-1 and glucagon receptors (Coskun 2022). Its half-life of about 6 days supports weekly dosing (Urva 2022). In phase 2, 48 weeks at 12 mg gave 24.2% weight loss in obesity (Jastreboff 2023) and lowered HbA1c in type 2 diabetes (Rosenstock 2023). In the phase 3 TRIUMPH-1 trial (n=2339, 80 weeks), 4, 9 and 12 mg gave 17.6%, 23.7% and 25.0% weight loss versus 3.9% with placebo, and reduced knee osteoarthritis pain and sleep apnea events (Jastreboff 2026). In TRIUMPH-2 (n=1152, obesity with type 2 diabetes), losses were 11.9 to 18.8% versus 5.1% (Bellido 2026). It is not approved by any regulator as of October 2026. ### Benefits Weight loss up to 25% at 80 weeks (human phase 3 RCT), weight loss and HbA1c reduction in type 2 diabetes (human phase 3 RCT), less knee osteoarthritis pain and sleep apnea events (human phase 3 RCT) ### Dosing reference - Research dose: 1 to 12 mg once weekly subcutaneously (phase 2 range; phase 3 used 4, 9 and 12 mg) - Range: 1000 to 12000 mcg, 1x weekly - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Investigational, not approved. Subcutaneous, once weekly. Phase 2 used 1 to 12 mg with escalation from 2 mg or lower (Jastreboff 2023); phase 3 TRIUMPH-1 and TRIUMPH-2 used 4, 9 or 12 mg for 80 weeks (Jastreboff 2026; Bellido 2026). ### Mechanism Retatrutide is a single peptide that activates the GIP, GLP-1 and glucagon receptors (Coskun 2022). GLP-1 and GIP receptor activation lower appetite and raise glucose-dependent insulin secretion; retatrutide also delays gastric emptying (Urva 2022). Glucagon receptor activation is proposed to raise energy expenditure and liver fat oxidation (Coskun 2022). A fatty-acid moiety binds albumin and extends the half-life to about 6 days (Urva 2022). ### Evidence Clinical: at least one published human trial or an approved drug - TRIUMPH-1 phase 3 (n=2339, 80 weeks, obesity without diabetes): 17.6%, 23.7% and 25.0% weight loss at 4, 9 and 12 mg versus 3.9% with placebo; less knee osteoarthritis pain and fewer apnea events (Jastreboff et al., 2026) - TRIUMPH-2 phase 3 (n=1152, obesity with type 2 diabetes, 80 weeks): 11.9%, 16.8% and 18.8% weight loss versus 5.1% with placebo (Bellido et al., 2026) - Phase 2 (n=338, 48 weeks): 24.2% weight loss at 12 mg versus 2.1% with placebo (Jastreboff et al., 2023) - Phase 1b in type 2 diabetes: dose-proportional PK, half-life about 6 days (Urva et al., 2022) - Human-trial status: phase 3 TRIUMPH programme reporting from 2026; not approved by FDA or EMA ### References - [Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff AM, Kaplan LM, Frías JP, et al., New England Journal of Medicine, 2023](https://doi.org/10.1056/NEJMoa2301972) - [Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Rosenstock J, Frias J, Jastreboff AM, et al., Lancet, 2023](https://doi.org/10.1016/S0140-6736(23)01053-X) - [LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun T, Urva S, Roell WC, et al., Cell Metabolism, 2022](https://doi.org/10.1016/j.cmet.2022.07.013) - [LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva S, Coskun T, Loh MT, et al., Lancet, 2022](https://doi.org/10.1016/S0140-6736(22)02033-5) - [Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. Jastreboff AM, Kaplan LM, Davies MJ, et al., New England Journal of Medicine, 2026](https://doi.org/10.1056/NEJMoa2604169) - [Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Bellido V, le Roux CW, Ekinci EI, et al., Lancet, 2026](https://doi.org/10.1016/S0140-6736(26)01861-1) - [Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats. Petersen J, Merrild C, Holm SK, et al., Nature Metabolism, 2026](https://doi.org/10.1038/s42255-026-01603-y) ### Side effects Gastrointestinal effects dominate and are dose-related: in TRIUMPH-2, diarrhoea affected 27 to 34% versus 13% on placebo and nausea 14 to 28% versus 8%. Hypotension (1 to 6% versus under 1%) and dysesthesia (4 to 7% versus 1%) were more frequent than placebo, and discontinuation for adverse events reached 12% at 9 mg (Bellido 2026). Phase 2 trials showed a dose-dependent heart rate rise (Jastreboff 2023). Delayed gastric emptying was measured in a dedicated study. Class risks of approved incretin drugs (pancreatitis, gallbladder disease, aspiration under anaesthesia) are expected but retatrutide has no label. ### Storage - Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 24+ months refrigerated - Reconstituted: 28 days refrigerated ### Pharmacology - Half-life: ~6 days (type 2 diabetes, subcutaneous; Urva 2022) - Bioavailability: Subcutaneous; absolute bioavailability not reported in located sources - Molecular weight: 4731.3 Da - Sequence: Y[Aib]QGTFTSDYSILLDKKAQ[Aib]AFIEYLLEGGPSSGAPPPS [one Lys lipidated with a fatty diacid; other non-coded residues per KEGG D12430] ### Stacks with - [Cagrilintide](https://peptidelabs.app/peptides/cagrilintide/) ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Rigin (Palmitoyl Tetrapeptide-7) URL: https://peptidelabs.app/peptides/rigin-palmitoyl-tetrapeptide-7/ Also known as: Palmitoyl Tetrapeptide-7, Palmitoyl Tetrapeptide-3, Pal-GQPR Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Palmitoyl tetrapeptide-7 (Pal-GQPR), a lipidated IgG fragment sold in the Matrixyl 3000 blend; IL-6 claims come from supplier data, and published human work tests only the blend. Strictly, rigin is the unmodified tetrapeptide Gly-Gln-Pro-Arg, a tuftsin-like fragment of human IgG that stimulated phagocytosis as strongly as tuftsin (Veretennikova et al., 1981); this record covers its palmitoylated form. Supplier data, repeated in reviews, say it lowers IL-6 and raises laminin and collagen VII (Resende et al., 2021). It is sold mainly with palmitoyl tripeptide-1 as Matrixyl 3000. Sederma authors reported improved dermal matrix structure versus placebo with that blend (Mondon et al., 2015), and it was detected in the stratum corneum of three volunteers (Trzaska et al., 2026). CIR found it safe in cosmetics at typical use under 10 ppm (Johnson et al., 2018). ### Benefits IL-6 reduction (supplier in vitro data, not peer reviewed), dermal matrix changes vs placebo with palmitoyl tripeptide-1 (supplier-run human study), stratum corneum uptake (human, n=3) ### Dosing reference - Research dose: Topical, typically under 10 ppm in finished products (CIR 2018); no trial-derived concentration for the peptide alone. Topical only, typically under 10 ppm (CIR). Human data are supplier-run and test it combined with palmitoyl tripeptide-1, as in Matrixyl 3000. ### Mechanism Proposed. The parent tetrapeptide GQPR is a tuftsin-like immunomodulator that stimulated phagocytosis in vitro (Veretennikova et al., 1981). For the palmitoylated form, the supplier reports lower IL-6 secretion, less UVB-induced inflammation and more laminin and collagen VII; these figures appear in reviews but not in peer-reviewed primary studies (Resende et al., 2021). Protection of collagen from inflammatory breakdown and reduced glycation have no published source. ### Evidence Preclinical: animal or in vitro data only - The unmodified tetrapeptide Gly-Gln-Pro-Arg, isolated from human IgG, stimulated phagocytosis as strongly as tuftsin (Veretennikova et al., 1981) - Blend with palmitoyl tripeptide-1 thinned the subepidermal low-echogenic band and improved dermal matrix structure vs placebo by confocal microscopy; Sederma-run (Mondon et al., 2015) - Detected in all stratum corneum layers, intercellularly, in 3 volunteers after a Matrixyl 3000 serum (Trzaska et al., 2026) - CIR panel: safe in cosmetics at present use, typically under 10 ppm (Johnson et al., 2018) - Human-trial status: no RCT of palmitoyl tetrapeptide-7 alone; human data are supplier-run blend studies ### References - [Rigin, another phagocytosis-stimulating tetrapeptide isolated from human IgG. Confirmations of a hypothesis. Veretennikova NI, Chipens GI, Nikiforovich GV, Betinsh YR, International journal of peptide and protein research, 1981](https://doi.org/10.1111/j.1399-3011.1981.tb02011.x) - [Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics. Johnson W, Bergfeld WF, Belsito DV, Hill RA, et al., International Journal of Toxicology, 2018](https://doi.org/10.1177/1091581818807863) - [Evaluation of dermal extracellular matrix and epidermal-dermal junction modifications using matrix-assisted laser desorption/ionization mass spectrometric imaging, in vivo reflectance confocal microscopy, echography, and histology: effect of age and peptide applications. Mondon P, Hillion M, Peschard O, Andre N, et al., Journal of cosmetic dermatology, 2015](https://doi.org/10.1111/jocd.12135) - [Permeation behaviour of cosmetic actives into the human stratum corneum. Trzaska AH, Kotowska AM, Starr NJ, Humphreys AJ, et al., International journal of pharmaceutics, 2026](https://doi.org/10.1016/j.ijpharm.2026.127447) - [Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, et al., Pharmaceuticals (Basel, Switzerland), 2021](https://doi.org/10.3390/ph14080702) ### Side effects CIR reviewed negative safety test data and found no concern at use concentrations under 10 ppm (Johnson et al., 2018). No systemic data exist. Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Topical (3 human volunteers, Matrixyl 3000 serum, 0.5 to 5 h): present in all stratum corneum layers, intercellular; dermal penetration not measured - Molecular weight: 694.92 Da - Sequence: Palmitoyl-Gly-Gln-Pro-Arg ### Stacks with - [Pal-GHK (Palmitoyl Tripeptide-1)](https://peptidelabs.app/peptides/pal-ghk-palmitoyl-tripeptide-1/) ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Selank URL: https://peptidelabs.app/peptides/selank/ Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Tuftsin-derived synthetic heptapeptide developed in Russia; small human trials report anxiolytic and mild nootropic effects without sedation or dependence. Selank is a synthetic heptapeptide combining the sequence of tuftsin with additional amino acids. Research shows anxiolytic and nootropic effects without sedation or addiction potential. Studies indicate benefits for anxiety, cognitive function, immune modulation, and stress resilience through GABA and serotonin pathway modulation. ### Benefits Stress reduction, mood improvement, cognitive enhancement ### Dosing reference - Research dose: Vendor/community range 250 to 500 mcg daily (intranasal or injection); not dose-tested. Russian anxiety trials used higher intranasal doses (see dosing notes). - Range: 250 to 500 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Usually intranasal. Russian anxiety trials used considerably higher intranasal doses than community protocols (roughly 1800-2700 mcg/day of a 0.15% solution). Generally well tolerated; transient nasal irritation and drowsiness reported. No long-term safety data outside Russia. ### Mechanism Proposed, from Russian rodent and in vitro work. Selank inhibited enkephalin-degrading enzymes (Zozulya et al., 2001), which the authors put forward as a basis for its anxiolytic action. In rodent brain it changed the expression of genes involved in GABAergic transmission (Volkova et al., 2016). Intranasal Selank raised BDNF expression in rat hippocampus (Inozemtseva et al., 2008). No single receptor target has been confirmed. ### Evidence Clinical: at least one published human trial or an approved drug - Selank was studied as an anxiolytic in generalized anxiety disorder and neurasthenia in a Russian trial (n=62) (Zozulia et al., 2008) - Selank was compared with phenazepam for anxiolytic effect and tolerability in anxiety disorders (n=60) (Medvedev et al., 2014) - A further Russian trial in anxiety disorders enrolled 70 patients (Medvedev et al., 2015) - Selank inhibited enkephalin-degrading enzymes (Zozulya et al., 2001) and raised hippocampal BDNF expression in rats after intranasal dosing (Inozemtseva et al., 2008) - Human-trial status: all human trials are Russian and published in Russian; Selank is a registered drug in Russia (Deigin et al., 2022). Outside Russia it turns up in seized unregulated research-peptide products (Vanhee et al., 2020) ### References - [Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zozulia AA, Neznamov GG, Siuniakov TS, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2008](https://pubmed.ncbi.nlm.nih.gov/18454096/) - [A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders. Medvedev VE, Tereshchenko ON, Israelian AIu, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2014](https://pubmed.ncbi.nlm.nih.gov/25176261/) - [Optimization of the treatment of anxiety disorders with selank. Medvedev VE, Tereshchenko ON, Kost NV, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2015](https://doi.org/10.17116/jnevro20151156133-40) - [The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Zozulya AA, Kost NV, Yu Sokolov O, et al., Bulletin of Experimental Biology and Medicine, 2001](https://doi.org/10.1023/a:1017979514274) - [Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Volkova A, Shadrina M, Kolomin T, et al., Frontiers in Pharmacology, 2016](https://doi.org/10.3389/fphar.2016.00031) - [Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Inozemtseva LS, Karpenko EA, Dolotov OV, et al., Doklady Biological Sciences, 2008](https://doi.org/10.1134/s0012496608040066) - [Development of Peptide Biopharmaceuticals in Russia. Deigin VI, Poluektova EA, Beniashvili AG, et al., Pharmaceutics, 2022](https://doi.org/10.3390/pharmaceutics14040716) - [The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind. Vanhee C, Francotte A, Janvier S, et al., Drug Testing and Analysis, 2020](https://doi.org/10.1002/dta.2717) ### Side effects Generally well tolerated in Russian clinical use; reported effects are limited to nasal irritation from the intranasal route, mild drowsiness, and occasional dizziness. Safety data outside Russian-language trials is limited. ### Pharmacology - Half-life: Not established in humans; no human plasma half-life published in the sources reviewed - Bioavailability: Not measured in humans. Intranasal dosing in rats raised hippocampal BDNF expression, evidence of central activity (Inozemtseva et al., 2008) - Molecular weight: 751.9 Da - Sequence: TKPRPGP ### Stacks with - [Dihexa](https://peptidelabs.app/peptides/dihexa/) - [Semax](https://peptidelabs.app/peptides/semax/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Semaglutide URL: https://peptidelabs.app/peptides/semaglutide/ Also known as: Ozempic, Wegovy, Rybelsus, NN9535 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Acylated GLP-1 receptor agonist; FDA-approved for type 2 diabetes (2017) and obesity (2021). In STEP 1, 2.4 mg weekly gave 14.9% weight loss at 68 weeks versus 2.4% with placebo. Semaglutide is a GLP-1(7-37) analog from Novo Nordisk with an Aib substitution at position 8 against DPP-4 breakdown and a C18 fatty diacid on Lys26 for albumin binding, giving a half-life of about one week (Lau 2015). In STEP 1, 2.4 mg weekly gave 14.9% weight loss over 68 weeks versus 2.4% (Wilding 2021); 7.2 mg gave 18.7% in STEP UP (Wharton 2025). SUSTAIN-6 (Marso 2016) and SELECT (Lincoff 2023) showed fewer cardiovascular events. FDA approvals: Ozempic for type 2 diabetes (2017), Rybelsus oral tablets (2019), Wegovy for weight (2021), with cardiovascular risk (2024), MASH (2025), Wegovy tablets (December 2025) and a 7.2 mg dose added later. All are marketed; one Ozempic presentation is discontinued. ### Benefits Weight loss (human RCTs; 14.9% at 2.4 mg, 18.7% at 7.2 mg), lower HbA1c in type 2 diabetes (human RCTs), 20% fewer major cardiovascular events in obesity (human RCT) ### Dosing reference - Research dose: 0.25 to 2.4 mg once weekly subcutaneously (label titration and usual maintenance); the label also allows 7.2 mg weekly for weight - Range: 250 to 7200 mcg, 1x weekly - Reconstitution: 3 mL bacteriostatic water - Common vial sizes: 3 mg, 5 mg Subcutaneous, once weekly, any time of day. Label titration starts at 0.25 mg weekly for 4 weeks and steps up every 4 weeks to the 2.4 mg maintenance dose; 7.2 mg is a labelled higher maintenance dose for weight. Oral forms (Rybelsus, Wegovy tablets) are taken daily on an empty stomach. With a one-week half-life, semaglutide stays in circulation 5 to 7 weeks after the last dose (Wegovy label). ### Mechanism Semaglutide binds and activates the GLP-1 receptor. It raises glucose-dependent insulin secretion, lowers glucagon, slows gastric emptying and reduces appetite and energy intake through central GLP-1 receptors (Wegovy label). It shares 94% sequence identity with human GLP-1. Aib at position 8 blocks DPP-4 degradation, Arg34 leaves one lysine for acylation, and a C18 fatty diacid with a hydrophilic spacer on Lys26 drives over 99% albumin binding, which slows clearance (Lau 2015; label). Direct vascular cardioprotection is proposed, not established. ### Evidence Clinical: at least one published human trial or an approved drug - STEP 1 (n=1961, 68 weeks): 2.4 mg weekly gave 14.9% weight loss versus 2.4% with placebo (Wilding et al., 2021) - STEP UP (n=1407, 72 weeks): 7.2 mg gave 18.7% weight loss versus 15.6% with 2.4 mg and 3.9% with placebo (Wharton et al., 2025) - SUSTAIN-6 (n=3297, type 2 diabetes): major cardiovascular events 6.6% versus 8.9%, hazard ratio 0.74 (Marso et al., 2016) - SELECT (n=17,604, obesity without diabetes): major cardiovascular events 6.5% versus 8.0%, hazard ratio 0.80 (Lincoff et al., 2023) - With cagrilintide (CagriSema, REDEFINE 1, n=3417): 20.4% weight loss at 68 weeks versus 3.0% with placebo (Garvey et al., 2025) - Status: FDA-approved and marketed. Ozempic (T2D, 2017), Rybelsus (oral, T2D, 2019), Wegovy (weight, 2021; CV risk 2024; MASH 2025; tablets 2025; 7.2 mg dose) ### References - [Once-Weekly Semaglutide in Adults with Overweight or Obesity. Wilding JPH, Batterham RL, Calanna S, et al., New England Journal of Medicine, 2021](https://doi.org/10.1056/NEJMoa2032183) - [Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. Marso SP, Bain SC, Consoli A, et al., New England Journal of Medicine, 2016](https://doi.org/10.1056/NEJMoa1607141) - [Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. Lau J, Bloch P, Schäffer L, et al., Journal of Medicinal Chemistry, 2015](https://doi.org/10.1021/acs.jmedchem.5b00726) - [Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al., New England Journal of Medicine, 2023](https://doi.org/10.1056/NEJMoa2307563) - [Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Wharton S, Freitas P, Hjelmesæth J, et al., Lancet Diabetes & Endocrinology, 2025](https://doi.org/10.1016/S2213-8587(25)00226-8) - [Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT, Blüher M, Osorto Contreras CK, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2502081) ### Side effects Nausea, vomiting, diarrhea, and constipation are the most common effects and are usually worst during dose escalation. Serious risks include pancreatitis, gallbladder disease and gallstones, and delayed gastric emptying that raises aspiration risk under anesthesia. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months refrigerated - Reconstituted: 56 days refrigerated ### Pharmacology - Half-life: ~1 week (subcutaneous, adults with overweight or obesity; present 5 to 7 weeks after last dose, Wegovy label) - Bioavailability: Subcutaneous 89% (Wegovy label); oral tablets reach much lower and more variable exposure (label) - Molecular weight: 4113.58 Da - Sequence: H[Aib]EGTFTSDVSSYLEGQAAK[spacer-C18 diacid]EFIAWLVRGRG ### Stacks with - [Cagrilintide](https://peptidelabs.app/peptides/cagrilintide/) ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Semax URL: https://peptidelabs.app/peptides/semax/ Also known as: ACTH (4-10) analog, Semax-1 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic ACTH(4-10) fragment (Met-Glu-His-Phe-Pro-Gly-Pro) developed in Russia; studied intranasally for attention, memory, and BDNF-linked neuroprotection. Semax is a synthetic heptapeptide analog of ACTH (4-10) with added Pro-Gly-Pro sequence. Research demonstrates nootropic, neuroprotective, and neurogenic properties. Studies show improvements in memory, attention, cognitive function, and potential benefits for stroke recovery and depression without hormonal side effects. ### Benefits Cognitive enhancement, focus, neuroprotection, memory, BDNF increase ### Dosing reference - Research dose: Vendor/community range 200 to 600 mcg daily (intranasal or injection); not dose-tested. Russian stroke trials used far higher doses (see dosing notes). - Range: 200 to 600 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Russian stroke trials used 12 mg/day (moderate) and 18 mg/day (severe) intranasally for 5 to 10 days (Gusev 1997) and 6,000 mcg/day for two 10-day courses after stroke (Gusev 2018), 20 to 30 times the community range. ACTH(4-10) analog with a Pro-Gly-Pro tail, so it lacks corticotropic activity. Usually intranasal. Nasal irritation and irritability are commonly reported (anecdotal). ### Mechanism Semax is ACTH(4-10) with a Pro-Gly-Pro C-terminal extension, which removes corticotropic activity. Intranasal Semax raised BDNF and trkB expression in rat hippocampus (Dolotov et al., 2006). It binds plasma membranes of the rat basal forebrain and is degraded slowly in their presence (Dolotov et al., 2004). In humans it changed default mode network connectivity on fMRI (Lebedeva et al., 2018). Effects on dopamine, serotonin, NGF and immune genes appear in the Russian literature but were not verified in this audit. ### Evidence Clinical: at least one published human trial or an approved drug - Semax raised BDNF and trkB expression in rat hippocampus (Dolotov et al., 2006) - Semax bound rat forebrain plasma membranes and its degradation half-life with membranes exceeded 1 h (Dolotov et al., 2004) - In acute hemispheric ischemic stroke, Russian patients received 12 to 18 mg/day in a clinical and electrophysiological study (Gusev et al., 1997) - Patients at different stages of ischemic stroke received 6000 mcg/day (Gusev et al., 2018) - Semax changed default mode network connectivity on fMRI (Lebedeva et al., 2018; Panikratova et al., 2020) - Human-trial status: human data are Russian stroke and fMRI studies; no trial outside Russia. Russian peptide drug registrations are reviewed in Deigin et al., 2022 ### References - [Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Dolotov OV, Karpenko EA, Inozemtseva LS, et al., Brain Research, 2006](https://doi.org/10.1016/j.brainres.2006.07.108) - [The binding of Semax, ACTH 4-10 heptapeptide, to plasma membranes of the rat forebrain basal nuclei and its biodegradation. Dolotov OV, Zolotarev IuA, Dorokhova EM, et al., Russian Journal of Bioorganic Chemistry, 2004](https://doi.org/10.1023/b:rubi.0000030127.46845.f0) - [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Gusev EI, Skvortsova VI, Miasoedov NF, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 1997](https://pubmed.ncbi.nlm.nih.gov/11517472/) - [The efficacy of semax in the tretament of patients at different stages of ischemic stroke. Gusev EI, Martynov MY, Kostenko EV, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018](https://doi.org/10.17116/jnevro20181183261-68) - [Effects of Semax on the Default Mode Network of the Brain. Lebedeva IS, Panikratova YR, Sokolov OY, et al., Bulletin of Experimental Biology and Medicine, 2018](https://doi.org/10.1007/s10517-018-4234-3) - [Functional Connectomic Approach to Studying Selank and Semax Effects. Panikratova YR, Lebedeva IS, Sokolov OY, et al., Doklady Biological Sciences, 2020](https://doi.org/10.1134/S001249662001007X) - [Development of Peptide Biopharmaceuticals in Russia. Deigin VI, Poluektova EA, Beniashvili AG, et al., Pharmaceutics, 2022](https://doi.org/10.3390/pharmaceutics14040716) ### Side effects Nasal irritation from the intranasal route, headache, and overstimulation or irritability at higher doses are the reported effects. Russian clinical use reports few adverse events, but independent safety data is limited. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Over 1 h for degradation in the presence of rat forebrain plasma membranes (in vitro; Dolotov et al., 2004); no human plasma half-life verified - Bioavailability: Not quantified in humans. Intranasal dosing raised hippocampal BDNF in rats, evidence of central activity (Dolotov et al., 2006) - Molecular weight: 813.93 Da - Sequence: Met-Glu-His-Phe-Pro-Gly-Pro ### Stacks with - [Dihexa](https://peptidelabs.app/peptides/dihexa/) - [Selank](https://peptidelabs.app/peptides/selank/) ### Categories - [Cognitive](https://peptidelabs.app/peptides/category/cognitive/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/) ## Sermorelin URL: https://peptidelabs.app/peptides/sermorelin/ Also known as: GHRH (1-29), GRF (1-29), Geref, Sermorelin acetate Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic GHRH(1-29) analog (Geref; FDA-approved 1997 for pediatric GH deficiency, withdrawn 2008 for commercial reasons) that restored GH and IGF-1 to young-adult levels in older men (n=10). Sermorelin is the 29-residue N-terminal fragment of human GHRH, the shortest fragment with full GHRH activity. It was approved by the FDA in 1997 (Geref, EMD Serono) for idiopathic GH deficiency in children at 30 mcg/kg nightly, and as a 1 mcg/kg IV diagnostic; the sponsor withdrew it in 2008 for commercial reasons, not safety. In healthy older men, 1 mg twice daily for 14 days restored 24 h GH and IGF-1 to young-adult levels (Corpas 1992, n=10). Single 2 mg nightly injections for 6 weeks raised nocturnal GH and two of six strength measures but did not change IGF-1 or body composition (Vittone 1997, n=11). A 16-week trial of a related analog at 10 mcg/kg nightly raised IGF-1 28% and activated B and T cells (Khorram 1997, n=19). No approved adult indication exists; adult use is compounded and off-label. ### Benefits GH and IGF-1 restoration in older men (human, n=10), nocturnal GH and some strength measures (human, n=11), immune-cell activation (human, n=19), height velocity in GH-deficient children (human, label indication) ### Dosing reference - Research dose: 0.5-2 mg SC per injection in adult trials (0.5-1 mg 2x daily, Corpas 1992; 2 mg nightly, Vittone 1997); pediatric label 30 mcg/kg nightly; research-community range 100-300 mcg nightly - Range: 500 to 2000 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Subcutaneous, given at bedtime in most adult trials; study durations ran 14 days to 16 weeks. Diagnostic use is a single 1 mcg/kg IV dose. Research protocols pair it with a GHRP; GHRH plus GHRP synergy is documented in men for GHRP-6 (Bowers 1990). Transient facial flushing and injection-site pain were the most common adverse events in trials (Prakash 1999). Intranasal bioavailability is 3-5%. ### Mechanism Sermorelin binds the GHRH receptor on anterior-pituitary somatotrophs, a Gs-coupled receptor that raises cAMP and triggers GH synthesis and release. It preserves the pulsatile pattern of GH secretion and the IGF-1 negative feedback loop (Corpas 1992). Plasma dipeptidyl peptidase IV cleaves the N-terminal Tyr-Ala, which is why the circulating half-life is a few minutes (Soule 1994). GHRPs act through the separate ghrelin receptor (GHS-R1a) and the two classes synergize (Bowers 1990). ### Evidence Clinical: at least one published human trial or an approved drug - Restored 24 h GH and IGF-1 in healthy old men to young-adult levels at 1 mg SC twice daily for 14 days (Corpas et al., 1992) - Single 2 mg nightly injections for 6 weeks raised nocturnal GH and some strength measures, no change in IGF-1 or body composition (Vittone et al., 1997) - [Nle27]GHRH(1-29) 10 mcg/kg nightly for 16 weeks raised IGF-1 28% and activated B and T lymphocytes in older adults (Khorram et al., 1997) - Increased height velocity in GH-deficient children at 30 mcg/kg nightly; 1 mcg/kg IV is a specific GH-deficiency test (Prakash and Goa, 1999) - Human-trial status: FDA-approved 1997 (Geref) for pediatric GH deficiency and diagnosis, withdrawn 2008 for commercial reasons; no approved adult indication ### References - [Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR, Journal of Clinical Endocrinology & Metabolism, 1992](https://doi.org/10.1210/jcem.75.2.1379256) - [Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Vittone J, Blackman MR, Busby-Whitehead J, et al., Metabolism, 1997](https://doi.org/10.1016/s0026-0495(97)90174-8) - [Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. Khorram O, Yeung M, Vu L, Yen SS, Journal of Clinical Endocrinology & Metabolism, 1997](https://doi.org/10.1210/jcem.82.11.4363) - [Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. Prakash A, Goa KL, BioDrugs, 1999](https://doi.org/10.2165/00063030-199912020-00007) - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration. Wilton P, Widlund L, Guilbaud O, Acta Paediatrica Supplement, 1993](https://doi.org/10.1111/j.1651-2227.1993.tb12827.x) - [Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?. Walker RF, Clinical Interventions in Aging, 2006](https://doi.org/10.2147/ciia.2006.1.4.307) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) ### Side effects Transient facial flushing and injection-site pain were the most common adverse events in pediatric and adult trials (Prakash 1999); no significant adverse effects in 6 weeks of 2 mg nightly dosing (Vittone 1997). Headache, dizziness, water retention, joint aches and reduced insulin sensitivity are commonly reported (anecdotal) with sustained GH elevation. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~4 min disappearance half-time (human, IV infusion; Soule 1994); GH stays elevated ~3 h after an IV dose (Wilton 1993) - Bioavailability: Intranasal 3-5% (human; Wilton 1993); SC absolute bioavailability not reported in located literature - Molecular weight: 3357.88 Da - Sequence: YADAIFTNSYRKVLGQLSARKLLQDIMSR[NH2] ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [GHRP-2](https://peptidelabs.app/peptides/ghrp-2/) - [GHRP-6](https://peptidelabs.app/peptides/ghrp-6/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) ## Sermorelin + Ipamorelin Blend URL: https://peptidelabs.app/peptides/sermorelin-ipamorelin-blend/ Also known as: Serm/Ipa, Anti-Aging GH Blend, Natural GH Stack Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of sermorelin (GHRH 1-29) and ipamorelin, 5 mg each; sermorelin raised GH and IGF-1 in older men, ipamorelin's only RCT was negative, and no study has tested the pair. Sermorelin was approved by FDA in 1997 as Geref for pediatric GH deficiency, and its US products were discontinued in 2008 for commercial reasons; this research blend is not that product. It mixes sermorelin and ipamorelin 5 mg each. Sermorelin at 1 mg twice daily restored GH and IGF-1 to young-adult levels in 10 older men (Corpas 1992), while 2 mg nightly raised nocturnal GH without changing body composition (Vittone 1997). Ipamorelin has one human PK study and one negative phase 2 trial in postoperative ileus (Beck 2014). GHRH(1-44) given with GHRP-6 was synergistic in men (Bowers 1990), the rationale for the pairing, but no study has tested sermorelin with ipamorelin. FDA lists ipamorelin in category 2 for 503B outsourcing on its compounding safety-risk page. ### Benefits GH and IGF-1 rise (human, sermorelin, small trials in older men); GH pulse after IV ipamorelin (human PK study); larger combined GH pulse expected from GHRH plus GHRP synergy (human, other analogs). No data for the blend ### Dosing reference - Research dose: 200 to 800 mcg of blend at bedtime (100 to 400 mcg of each at the 5 mg/5 mg ratio): vendor/community range, no published human dose of the blend. Adult sermorelin trials used 0.5 to 2 mg per injection - Range: 200 to 800 mcg, 1x daily before bed - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg Subcutaneous at bedtime in community use, continuously or 5 days on, 2 days off; neither pattern has been studied for the blend. Adult sermorelin trials used 0.5 to 1 mg twice daily (Corpas 1992) or 2 mg nightly (Vittone 1997), above the 100 to 400 mcg of sermorelin in this range; the pediatric label dose was 30 mcg/kg nightly. Human ipamorelin doses were IV (0.03 mg/kg twice daily in the ileus trial). ### Mechanism Proposed, from component and class studies. Sermorelin is GHRH(1-29) amide, the shortest fully active fragment of GHRH, acting on the pituitary GHRH receptor; it is cleared within minutes in men. Ipamorelin is a ghrelin-receptor agonist that released GH without raising ACTH or cortisol in swine (Raun 1998). GHRH-receptor and ghrelin-receptor agonists given together raise GH more than either alone in men (Bowers 1990), shown with GHRH(1-44) and GHRP-6 rather than this pair. Claims that the blend restores a more natural GH pattern, or suits long-term use better than other combinations, have no published source. ### Evidence Preclinical: animal or in vitro data only - Sermorelin 1 mg SC twice daily for 14 days restored 24 h GH and IGF-1 in healthy older men to young-adult levels (Corpas et al., 1992) - Sermorelin 2 mg nightly for 6 weeks raised nocturnal GH and some strength measures, with no change in IGF-1 or body composition (Vittone et al., 1997) - IV ipamorelin in 40 healthy men gave a single GH peak at 40 min with a 2 h terminal half-life (Gobburu et al., 1999) - Phase 2 RCT of IV ipamorelin in postoperative ileus (n=114): well tolerated, no efficacy difference from placebo (Beck et al., 2014) - Human-trial status: no study has tested the blend as sold. Sermorelin was approved in 1997 (Geref) for pediatric GH deficiency and discontinued in 2008; GHRH plus GHRP synergy in men was shown with GHRH(1-44) and GHRP-6, not this pair (Bowers et al., 1990) ### References - [Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR, Journal of Clinical Endocrinology & Metabolism, 1992](https://doi.org/10.1210/jcem.75.2.1379256) - [Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Vittone J, Blackman MR, Busby-Whitehead J, et al., Metabolism, 1997](https://doi.org/10.1016/s0026-0495(97)90174-8) - [Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. Prakash A, Goa KL, BioDrugs, 1999](https://doi.org/10.2165/00063030-199912020-00007) - [Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994](https://doi.org/10.1210/jcem.79.4.7962295) - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) - [Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999](https://doi.org/10.1023/a:1018955126402) - [Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014](https://doi.org/10.1007/s00384-014-2030-8) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) ### Side effects No human safety study of the blend has been published. In sermorelin trials, transient facial flushing and injection-site pain were the most common adverse events (Prakash 1999); IV ipamorelin was well tolerated in a phase 2 trial (Beck 2014). Commonly reported by users (anecdotal): injection-site reactions, flushing, head rush, water retention and joint aches; reduced insulin sensitivity and carpal tunnel symptoms are reported with sustained GH elevation. Ipamorelin is in category 2 of FDA's 503B interim policy (added 2023-09-29) and in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Sermorelin ~4 min (human, IV infusion). Ipamorelin ~2 h terminal (human, IV) - Bioavailability: Not reported for subcutaneous dosing of either component in the sources reviewed; human ipamorelin data are IV. No data for the blend ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## SLU-PP-332 URL: https://peptidelabs.app/peptides/slu-pp-332/ Also known as: 4-Hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide, SR9861, CAS 303760-60-3, ERR pan-agonist 332 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Small-molecule ERR-alpha/beta/gamma pan-agonist studied as an exercise mimetic; shown in mice to switch on exercise-like gene programs, raising fat oxidation and endurance. SLU-PP-332 is a small-molecule pan-agonist of the estrogen-related receptors ERRalpha, beta and gamma, developed as a chemical tool and exercise mimetic. In the first report it activated all three isoforms with highest potency at ERRalpha, raised mitochondrial function and cellular respiration in a muscle cell line, and in mice increased type IIa oxidative fibres and treadmill endurance through an ERRalpha-dependent acute aerobic exercise gene program (Billon 2023). In diet-induced obese and ob/ob mice it raised energy expenditure and fat oxidation, reduced fat mass and improved insulin sensitivity (Billon 2024). It improved ejection fraction, fibrosis and survival in a mouse pressure-overload heart failure model (Xu 2024) and reduced mitochondrial dysfunction in the aging mouse kidney (Wang 2023). All in vivo data are rodent and intraperitoneal; no human trials exist. ### Benefits Increased fat oxidation, endurance capacity, metabolic support (rodent studies only) ### Dosing reference - Research dose: 10-50 mg (vendor range; no published human or dose-finding data, and the compound is not orally bioavailable) - Range: 10000 to 50000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 10 mg, 50 mg Research chemical, not a peptide. All in vivo data are rodent and intraperitoneal (Billon 2023; Billon 2024). The compound is not orally bioavailable, which is why its developers built SLU-PP-915 (Billon 2026). No human pharmacokinetic, dose-finding or safety data exist, so any human dose is extrapolation. The 10-50 mg figures in this record are a vendor range with no published basis. ### Mechanism SLU-PP-332 is a synthetic agonist of the orphan nuclear receptors ERRalpha, ERRbeta and ERRgamma, with the highest potency at ERRalpha (Billon 2023). ERRs regulate genes for mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation and the Krebs cycle (Billon 2026). In a skeletal muscle cell line the compound raised mitochondrial function and cellular respiration, and in mice it induced an ERRalpha-specific acute aerobic exercise gene program; ERRalpha activation was required for the endurance effect, shown with knockouts (Billon 2023). In mouse heart, ERR agonism raised fatty acid metabolism and mitochondrial gene expression (Xu 2024). Reported effects on PGC-1alpha coactivation are downstream observations in rodent and cell work, not a demonstrated binding target. ### Evidence Preclinical: animal or in vitro data only - Pan-ERR agonist with highest potency at ERRalpha; increased type IIa oxidative muscle fibres and treadmill endurance in mice, and the effect required ERRalpha (Billon et al., 2023) - In diet-induced obese and ob/ob mice, treatment raised energy expenditure and fatty acid oxidation, reduced fat mass accumulation and improved insulin sensitivity (Billon et al., 2024) - Improved ejection fraction, reduced fibrosis and increased survival in mouse pressure-overload heart failure, without changing cardiac hypertrophy (Xu et al., 2024) - Reversed markers of mitochondrial dysfunction and inflammation in the aging mouse kidney (Wang et al., 2023) - In myoblasts cultured from muscle biopsies of inactive women, treatment altered metabolic and mitochondrial markers in vitro (Bonanni et al., 2025) - Human-trial status: none. No clinical trial of SLU-PP-332 is registered or published; the compound lacks oral bioavailability and a successor, SLU-PP-915, was developed for that reason (Billon et al., 2026). Anti-doping laboratories have published detection methods, so it is treated as a doping agent (Möller et al., 2026; Avliyakulov et al., 2026) ### References - [Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. Billon C, Sitaula S, Banerjee S, et al., ACS Chemical Biology, 2023](https://doi.org/10.1021/acschembio.2c00720) - [A Synthetic ERR Agonist Alleviates Metabolic Syndrome. Billon C, Schoepke E, Avdagic A, et al., Journal of Pharmacology and Experimental Therapeutics, 2024](https://doi.org/10.1124/jpet.123.001733) - [Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Xu W, Billon C, Li H, et al., Circulation, 2024](https://doi.org/10.1161/CIRCULATIONAHA.123.066542) - [Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney. Wang XX, Myakala K, Libby AE, et al., American Journal of Pathology, 2023](https://doi.org/10.1016/j.ajpath.2023.07.008) - [An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. Billon C, Appourchaux K, Côté I, Burris TP, Journal of Pharmacology and Experimental Therapeutics, 2026](https://doi.org/10.1016/j.jpet.2025.103787) - [Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. Bonanni R, Falvino A, Matticari A, et al., Frontiers in Physiology, 2025](https://doi.org/10.3389/fphys.2025.1616693) - [In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential. Möller T, Krug O, Thevis M, Rapid Communications in Mass Spectrometry, 2026](https://doi.org/10.1002/rcm.70039) - [Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes. Avliyakulov NK, Sobolevsky T, Ahrens E, et al., Drug Testing and Analysis, 2026](https://doi.org/10.1002/dta.70035) ### Side effects No human safety data of any kind. All in vivo work is rodent and intraperitoneal, and none of the published studies was designed as a toxicology study (Billon 2023; Billon 2024; Xu 2024). Human pharmacokinetics and the effects of sustained ERR agonism in humans are uncharacterised. The compound is not orally bioavailable (Billon 2026). ### Storage - Storage: Refrigerate 2-8°C (36-46°F); general research-powder guidance, no compound-specific CoA located - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: No half-life value published; the original report states only that intraperitoneal exposure in mice is sufficient to use the compound in vivo (Billon 2023). No human pharmacokinetic data. - Bioavailability: Not orally bioavailable; its developers state SLU-PP-332 'lacks oral bioavailability' and designed SLU-PP-915 to fix that (Billon 2026). Rodent studies dosed intraperitoneally (Billon 2023). - Molecular weight: 290.32 Da - Sequence: N/A - small molecule ERR agonist (not a peptide) ### Stacks with - [MOTS-c](https://peptidelabs.app/peptides/mots-c/) - [AICAR](https://peptidelabs.app/peptides/aicar/) ### Categories - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) ## SNAP-8 URL: https://peptidelabs.app/peptides/snap-8/ Also known as: Acetyl Octapeptide-3, Acetyl Octapeptide-1, Acetyl Glutamyl Heptapeptide-3, SNAP8 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Acetylated octapeptide (Ac-EEMQRRAD-NH2, acetyl octapeptide-3) that extends the Argireline sequence by two residues; human data come only from multi-ingredient products such as microneedle patches. SNAP-8 is Lipotec's (now Lubrizol's) acetyl octapeptide-3, the Argireline hexapeptide with Ala-Asp added at the C-terminus. The efficacy figures in circulation are manufacturer data: a review quotes 43% inhibition of glutamate release at 1.5 mM and wrinkle reduction of up to 62% (Errante et al., 2020), while another company figure is up to 38%, mean 7.1%, from a 28-day split-face test (Moy et al., 2023). Published human studies tested the peptide only inside combination products: a placebo-patch-controlled microneedle study in 24 people (Shin et al., 2024), an uncontrolled 12-week patch study (Avcil et al., 2020) and a multi-ingredient serum (Moy et al., 2023). No study isolates the peptide's own effect. The old '63% in 28 days' figure has no published source. ### Benefits Expression-line reduction (manufacturer data, not peer reviewed), eye-wrinkle improvement from a combination microneedle patch (human, multi-ingredient), no cytotoxicity of nanoparticle-loaded peptide (in vitro) ### Dosing reference - Research dose: Topical. Published products used 0.03% peptide in a microneedle patch, or a cream with 3% of a 0.05% peptide solution in a company test; the old 3 to 10% figure has no source. Topical only. In the one controlled study the peptide was delivered by an overnight dissolving microneedle patch at 0.03%, not a cream. A company split-face test used a cream with 3% of a 0.05% peptide solution twice daily for 28 days. Percentages for trade solutions and pure peptide differ by orders of magnitude. ### Mechanism Proposed, and inferred from the parent hexapeptide. Acetyl hexapeptide-3 (Argireline) mimics the N-terminus of SNAP-25 and competes for a place in the SNARE complex, lowering catecholamine release from chromaffin cells in vitro (Blanes-Mira et al., 2002). SNAP-8 adds two SNAP-25 residues, and the manufacturer reports stronger inhibition of glutamate release in vitro (Errante et al., 2020); that comparison is not peer reviewed. No study has measured SNARE assembly, acetylcholine release or muscle activity after topical SNAP-8. The parent peptide barely crosses human skin in vitro (Kraeling et al., 2015), so whether a cream reaches the neuromuscular junction is unknown. ### Evidence Preclinical: animal or in vitro data only - Microneedle patch with 0.03% acetyl octapeptide-3, ascorbyl glucoside and cyclic lysophosphatidic acid improved eye wrinkles, TEWL and elasticity over 28 days versus a hyaluronic-acid-only patch in 24 people (Shin et al., 2024) - Microneedle patch combining acetyl octapeptide-3, palmitoyl tripeptide-5 and other actives: 25.8% decrease in fine lines at 12 weeks, uncontrolled (Avcil et al., 2020) - Manufacturer data quoted in reviews: 43% glutamate-release inhibition at 1.5 mM in vitro and up to 62% wrinkle reduction (Errante et al., 2020); a company split-face test is cited at up to 38%, mean 7.1% (Moy et al., 2023) - Peptide-loaded polymer nanoparticles reached 220.69 mg/g loading and were not cytotoxic in vitro (Baglamis et al., 2023) - Human-trial status: no published trial of SNAP-8 alone; human data come from combination products, mostly run by their manufacturers ### References - [Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Errante F, Ledwoń P, Latajka R, Rovero P, et al., Frontiers in chemistry, 2020](https://doi.org/10.3389/fchem.2020.572923) - [Clinical Safety and Efficacy Evaluation of a Dissolving Microneedle Patch Having Dual Anti-Wrinkle Effects With Safe and Long-Term Activities. Shin JY, Han D, Yoon KY, Jeong DH, et al., Annals of dermatology, 2024](https://doi.org/10.5021/ad.23.136) - [Efficacy of bioactive peptides loaded on hyaluronic acid microneedle patches: A monocentric clinical study. Avcil M, Akman G, Klokkers J, Jeong D, et al., Journal of cosmetic dermatology, 2020](https://doi.org/10.1111/jocd.13009) - [Peptide-pro complex serum: Investigating effects on aged skin. Moy M, Diaz I, Lesniak E, Giancola G, Journal of cosmetic dermatology, 2023](https://doi.org/10.1111/jocd.14992) - [A synthetic hexapeptide (Argireline) with antiwrinkle activity. Blanes-Mira C, Clemente J, Jodas G, Gil A, et al., International journal of cosmetic science, 2002](https://doi.org/10.1046/j.1467-2494.2002.00153.x) - [In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation. Kraeling ME, Zhou W, Wang P, Ogunsola OA, Cutaneous and ocular toxicology, 2015](https://doi.org/10.3109/15569527.2014.894521) - [New insight into anti-wrinkle treatment: Using nanoparticles as a controlled release system to increase acetyl octapeptide-3 efficiency. Baglamis S, Feyzioğlu-Demir E, Akgöl S, Polymer Bulletin, 2023](https://doi.org/10.1007/s00289-022-04663-8) ### Side effects No adverse effects reported in a 28-day study of a combination microneedle patch (n=24) (Shin et al., 2024) or a 12-week combination patch study (Avcil et al., 2020). Nanoparticle-loaded peptide was not cytotoxic in vitro (Baglamis et al., 2023). No single-ingredient safety study has been published. Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured. The parent hexapeptide reached 0.01% of an applied dose in the epidermis of human skin in vitro and none in the dermis (Kraeling et al., 2015); penetration to muscle is unproven - Molecular weight: 1075.16 Da - Sequence: [Ac]-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-[NH2] ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## SS-31 (Elamipretide) URL: https://peptidelabs.app/peptides/ss-31-elamipretide/ Also known as: Elamipretide, FORZINITY, Bendavia, MTP-131, elamipretide hydrochloride Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Mitochondria-targeted tetrapeptide that binds cardiolipin. FDA granted accelerated approval on 2025-09-19 as FORZINITY, 40 mg subcutaneously once daily, to improve muscle strength in Barth syndrome. Elamipretide (SS-31, MTP-131, formerly Bendavia) is an aromatic-cationic tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, that concentrates in the inner mitochondrial membrane and binds cardiolipin. FDA granted accelerated approval on 2025-09-19 as FORZINITY for Barth syndrome, at 40 mg subcutaneously once daily in patients weighing at least 30 kg, on an intermediate endpoint of knee extensor strength, with continued approval contingent on a confirmatory trial. The trial record elsewhere is largely negative: the Barth crossover trial missed both primary endpoints and the gains appeared only in the open-label extension (Thompson 2021, 2024), the phase 3 MMPOWER-3 trial in 218 primary mitochondrial myopathy patients missed both primaries (Karaa 2023), and two heart failure trials failed to improve left ventricular end-systolic volume (Daubert 2017; Butler 2020). ### Benefits Improved knee extensor muscle strength in Barth syndrome (basis of the FDA accelerated approval, n=12 plus extension), sustained 6-minute walk gains in that extension, reduced oxidative stress and better mitochondrial function (rodent and cell). Anti-aging claims are rodent-only ### Dosing reference - Research dose: 40 mg subcutaneously once daily, the approved dosage for patients weighing at least 30 kg; 20 mg once daily in adults with eGFR under 30 mL/min not on dialysis - Range: 20000 to 40000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 20 mg, 40 mg Subcutaneous injection into the abdomen at least 2 inches from the navel, or the outer thigh, rotating sites daily; the approved product is a ready-to-use 280 mg/3.5 mL solution (80 mg/mL) needing no reconstitution, and each 0.5 mL dose delivers 40 mg. Vials are discarded 8 days after first opening. Trial doses: 40 mg/day subcutaneously in Barth syndrome and in MMPOWER-3; 4 mg and 40 mg/day for 28 days in PROGRESS-HF; single 4-hour infusions at 0.005 to 0.25 mg/kg/h in the earlier heart failure study. Research-grade lyophilized vials require reconstitution and are not the approved product. ### Mechanism FDA's label describes elamipretide as a mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane and improves mitochondrial morphology and function. Its alternating aromatic-cationic structure drives accumulation there. Mechanistic work refines this: the peptide binds lipid bilayers and modulates membrane surface electrostatics, which the authors propose as the key component of its action rather than a specific protein target (Mitchell 2020), and a genome-wide CRISPR screen identified phospholipid scramblase 3 as a biological target in kidney cells, reported in 2024. In Barth syndrome, treatment moved the monolysocardiolipin to cardiolipin ratio in a direction that tracked clinical outcomes (Thompson 2024). Effects on reactive oxygen species are reported in cell and rodent models. ### Evidence Clinical: at least one published human trial or an approved drug - TAZPOWER, a randomized double-blind placebo-controlled crossover trial of 40 mg/day in 12 Barth syndrome patients, missed both primary endpoints (6-minute walk distance and symptom score); in the open-label extension, 6-minute walk distance improved by a cumulative 96.1 m at week 168 and knee extensor strength rose, which became the basis of the accelerated approval (Thompson et al., 2021; Thompson et al., 2024) - MMPOWER-3, a phase 3 randomized trial of 40 mg/day for 24 weeks in 218 primary mitochondrial myopathy patients, missed both primary endpoints; the 6-minute walk difference was -3.2 m and the fatigue score difference was not significant, graded Class I evidence of no effect (Karaa et al., 2023) - PROGRESS-HF randomized 71 patients with reduced ejection fraction to placebo, 4 mg or 40 mg daily for 28 days: left ventricular end-systolic volume and ejection fraction did not differ from placebo (Butler et al., 2020) - An earlier ascending-dose trial of single 4-hour infusions in 36 patients with reduced ejection fraction found reduced left ventricular end-diastolic and end-systolic volumes at end of infusion with no serious adverse events, and plasma levels undetectable by 24 hours (Daubert et al., 2017) - ReCLAIM-2, a randomized phase 2 trial in age-related macular degeneration with geographic atrophy, evaluated lesion growth, visual function and ellipsoid zone preservation (Ehlers et al., 2025) - Human-trial status: FDA granted accelerated approval on 2025-09-19 for Barth syndrome only, on an intermediate endpoint, with continued approval contingent on a confirmatory trial. The approval rests on 12 patients and their extension. Trials in primary mitochondrial myopathy and heart failure were negative ### References - [Elamipretide: First Approval. Shirley M, Drugs, 2026](https://doi.org/10.1007/s40265-025-02269-8) - [A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Thompson WR (published as Reid Thompson W), Hornby B, Manuel R, Bradley E, et al., Genetics in Medicine, 2021](https://doi.org/10.1038/s41436-020-01006-8) - [Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Thompson WR, Manuel R, Abbruscato A, Carr J, et al., Genetics in Medicine, 2024](https://doi.org/10.1016/j.gim.2024.101138) - [Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Karaa A, Bertini E, Carelli V, Cohen BH, et al., Neurology, 2023](https://doi.org/10.1212/WNL.0000000000207402) - [Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. Butler J, Khan MS, Anker SD, Fonarow GC, et al., Journal of Cardiac Failure, 2020](https://doi.org/10.1016/j.cardfail.2020.02.001) - [Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. Daubert MA, Yow E, Dunn G, Marchev S, et al., Circulation: Heart Failure, 2017](https://doi.org/10.1161/CIRCHEARTFAILURE.117.004389) - [The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. Mitchell W, Ng EA, Tamucci JD, Boyd KJ, et al., Journal of Biological Chemistry, 2020](https://doi.org/10.1074/jbc.RA119.012094) - [ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. Ehlers JP, Hu A, Boyer D, Cousins SW, et al., Ophthalmology Science, 2025](https://doi.org/10.1016/j.xops.2024.100628) ### Side effects Injection-site reactions dominate. In the placebo-controlled crossover period, all 12 patients on elamipretide had a local administration reaction against 8 of 12 on placebo: injection-site erythema 12 of 12 versus 3 of 12, induration and pruritus 8 of 12 versus 2 of 12, pain 9 of 12 versus 5 of 12, bruising and urticaria 3 of 12 versus 0. Eosinophil counts rose frequently when dosing ran 30 days or longer, peaking around day 90 at a mean increase of 0.5 to 0.6 times 10 to the ninth per litre and returning to baseline after 6 to 12 months or on stopping, with no clinical consequence reported. No clinically significant QTc prolongation at 3 times the peak concentration of the approved dose. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: Approved product: not reconstituted; the opened vial is discarded 8 days after first use and may be held at 2 to 8 C or at 20 to 25 C in that window. Research lyophilized powder: 28 to 30 days refrigerated after reconstitution is vendor guidance ### Pharmacology - Half-life: Not stated in the FDA label. Peak concentration 0.5 to 1 h after subcutaneous dosing, minimal accumulation on daily dosing, and about 100% of the dose recovered in urine as parent plus the inactive M1 and M2 metabolites by 48 h. After a 4-hour infusion, plasma levels were undetectable by 24 h - Bioavailability: Subcutaneous: approximately 92% absolute bioavailability, with comparable exposure from thigh or abdomen; volume of distribution about 0.5 L/kg and plasma protein binding about 39% (FDA label) - Molecular weight: 639.8 Da - Sequence: D-Arg-Dmt-Lys-Phe-NH2 ### Categories - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) ## Survodutide URL: https://peptidelabs.app/peptides/survodutide/ Also known as: BI 456906 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Glucagon and GLP-1 receptor dual agonist peptide (BI 456906); in phase 3 SYNCHRONIZE-1, 3.6 and 6.0 mg weekly cut body weight 12.2 to 13.0% vs 5.4% with placebo at 76 weeks. Survodutide (BI 456906) is a 29-residue glucagon-based peptide from Boehringer Ingelheim with GLP-1 receptor activity built into the glucagon sequence, 1-aminocyclobutane-1-carboxylic acid at position 2 against DPP-4 cleavage, and a C18 diacid on Lys24 for once-weekly subcutaneous dosing (Zimmermann 2022). In a 46-week phase 2 obesity trial (n=386), weight fell 6.2 to 14.9% across 0.6 to 4.8 mg vs 2.8% with placebo (le Roux 2024). In biopsy-confirmed MASH with F1 to F3 fibrosis, 47 to 62% improved without fibrosis worsening vs 14% (Sanyal 2024). Phase 3: 12.2 to 13.0% weight loss vs 5.4% at 76 weeks without diabetes, 8.2 to 9.8% vs 3.9% with type 2 diabetes, and 30% or more liver-fat reduction in 68.5% vs 28.6% in at-risk MASLD. Investigational; no approval in Drugs@FDA. ### Benefits Weight loss (human phase 3 RCTs), reduced liver fat in at-risk MASLD (human phase 3 RCT), MASH improvement without fibrosis worsening (human phase 2 RCT), lower HbA1c in type 2 diabetes (human phase 3 RCT) ### Dosing reference - Research dose: 3.6 or 6.0 mg once weekly in phase 3 (SYNCHRONIZE); phase 2 tested 0.6 to 4.8 mg (obesity) and 2.4 to 6.0 mg (MASH) - Range: 2400 to 6000 mcg, 1x weekly - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg Subcutaneous, once weekly. Phase 2 obesity: 20 weeks of dose escalation, then 26 weeks of maintenance (le Roux 2024). Phase 2 MASH: 24-week rapid escalation, then 24 weeks of maintenance (Sanyal 2024). Phase 3 escalated to 3.6 or 6.0 mg and treated for 76 weeks (le Roux 2026; Wharton 2026). No dose adjustment was needed in cirrhosis in a phase 1 PK study (Lawitz 2024). ### Mechanism Survodutide is a dual agonist of the glucagon receptor and the GLP-1 receptor, made by introducing GLP-1 receptor activity into the human glucagon sequence and tuning the balance between the two (Zimmermann 2022). In mice it lowered body weight more than semaglutide, through both reduced food intake and raised energy expenditure; glucagon receptor engagement in the liver is proposed to drive the extra liver-fat reduction (Zimmermann 2022). In people it lowered plasma amino acids and glucagon, read as target engagement at both receptors (Jungnik 2023). A C18 diacid on a glycine-serine linker at Lys24 binds albumin to extend the half-life (Zimmermann 2022). ### Evidence Clinical: at least one published human trial or an approved drug - Phase 1b, up to 16 weeks (n=125): placebo-corrected weight loss up to 13.8%; lower plasma amino acids and glucagon showed target engagement (Jungnik et al., 2023) - Phase 2 obesity, 46 weeks (n=386): -6.2% to -14.9% across 0.6 to 4.8 mg vs -2.8% with placebo; GI events 75% vs 42% (le Roux et al., 2024) - Phase 2 MASH with F1 to F3 fibrosis, 48 weeks (n=293): MASH improvement without fibrosis worsening in 47 to 62% vs 14% with placebo (Sanyal et al., 2024) - Phase 3 SYNCHRONIZE-1, 76 weeks (n=725, no diabetes): -12.2% (3.6 mg) and -13.0% (6.0 mg) vs -5.4% with placebo (le Roux et al., 2026); SYNCHRONIZE-2 with type 2 diabetes (n=752): -8.2% and -9.8% vs -3.9% (Wharton et al., 2026) - Phase 3 SYNCHRONIZE-MASLD, 48 weeks (n=216): 30% or more liver-fat reduction by MRI-PDFF in 68.5% vs 28.6% with placebo, treatment-regimen estimand (Kaplan et al., 2026) - Human-trial status: phase 3 reported for obesity, type 2 diabetes and MASLD; a cardiovascular outcomes trial (SYNCHRONIZE-CVOT) is under way; no approval in Drugs@FDA as of October 2026 ### References - [BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Zimmermann T, Thomas L, Baader-Pagler T, et al., Molecular Metabolism, 2022](https://doi.org/10.1016/j.molmet.2022.101633) - [Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Jungnik A, Arrubla Martinez J, Plum-Mörschel L, et al., Diabetes, Obesity and Metabolism, 2023](https://doi.org/10.1111/dom.14948) - [Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. le Roux CW, Steen O, Lucas KJ, et al., The Lancet Diabetes & Endocrinology, 2024](https://doi.org/10.1016/S2213-8587(23)00356-X) - [A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. Sanyal AJ, Bedossa P, Fraessdorf M, et al., New England Journal of Medicine, 2024](https://doi.org/10.1056/NEJMoa2401755) - [Survodutide Once Weekly for the Treatment of Adults with Obesity. le Roux CW, Wharton S, Startseva E, et al., New England Journal of Medicine, 2026](https://doi.org/10.1056/NEJMoa2600751) - [Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes. Wharton S, le Roux CW, Startseva E, et al., New England Journal of Medicine, 2026](https://doi.org/10.1056/NEJMoa2607219) - [Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial. Kaplan LM, Startseva E, le Roux CW, et al., Nature Medicine, 2026](https://doi.org/10.1038/s41591-026-04479-3) - [Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis. Lawitz EJ, Fraessdorf M, Neff GW, et al., Journal of Hepatology, 2024](https://doi.org/10.1016/j.jhep.2024.06.003) ### Side effects Gastrointestinal events are the main effect: 75% vs 42% on placebo in phase 2 obesity (le Roux 2024); nausea 66%, diarrhoea 49% and vomiting 41% vs 23%, 23% and 4% in phase 2 MASH, with serious adverse events 8% vs 7% (Sanyal 2024); 80.9 to 89.7% vs 47.9% in SYNCHRONIZE-1, mostly mild to moderate. In phase 1b with 6-week escalation, 12.5% stopped, most often for a cardiac or vascular event (7.5%) (Jungnik 2023). No deaths in SYNCHRONIZE-1. ### Storage - Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 24+ months refrigerated - Reconstituted: 28 days refrigerated (general lyophilised-peptide guidance) ### Pharmacology - Half-life: Human value not given in published abstracts; mean residence time 44 h (mouse) and 140 h (dog) after subcutaneous dosing; dosed once weekly in humans - Bioavailability: No figure published; subcutaneous tmax 7 h (mouse) and 51 h (dog) (Zimmermann 2022) - Molecular weight: 4231.7 Da - Sequence: H[Ac4c]QGTFTSDYSKYLDERAAKDFIK[C18 diacid-gamma-Glu-GSGSGG on Lys24]WLESA-NH2 ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Syn-AKE URL: https://peptidelabs.app/peptides/syn-ake/ Also known as: Dipeptide Diaminobutyroyl Benzylamide Diacetate, SYN-AKE, DABBA, Tripeptide-3 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Small peptidomimetic (beta-Ala-Pro-Dab benzylamide, sold as the diacetate) modeled on viper waglerin-1; one manufacturer-run RCT (n=57) found less forehead frown-line area at 4 weeks. Syn-AKE (INCI dipeptide diaminobutyroyl benzylamide diacetate) is a small synthetic molecule from Pentapharm, now DSM, built from beta-alanine, proline and diaminobutyric acid benzylamide. It is described as a mimic of waglerin-1, a 22-residue peptide from Tropidolaemus wagleri venom (Debono et al., 2017). The one published randomized, double-blind, placebo-controlled trial was run by DSM: 57 adults aged 50 to 65 applied 4% of a trade product holding 2500 ppm of the compound twice daily, and after 4 weeks the active group had less forehead wrinkle area and length when frowning (Campiche et al., 2021). The '52% in 28 days' figure is manufacturer data with no published trial behind it (Errante et al., 2020). Other human data come from a L'Oreal serum that also contains acetyl hexapeptide-8 (Zhu et al., 2026). ### Benefits Forehead frown-line area and length reduction at 4 weeks (human RCT, manufacturer-run, n=57), antioxidant activity and predicted MMP and SIRT1 binding (in vitro, in silico); muscle relaxation itself is unmeasured ### Dosing reference - Research dose: Topical. 4% of a trade product containing 2500 ppm of the compound (about 0.01% compound) in the one published RCT; a combination serum lists 2%. Topical only. The RCT applied a nickel-sized amount (2 mg/cm2) over the whole face twice daily for 4 weeks, using 4% of a trade product that holds 2500 ppm of the compound. A combination serum used alongside botulinum toxin injections lists 2% of the ingredient (Lupin et al., 2024). ### Mechanism Proposed, by analogy to the parent toxin. Waglerin-1 is a competitive antagonist of the adult (epsilon-subunit) muscle nicotinic acetylcholine receptor; it blocked end-plate responses in adult mice with an IC50 of 50 nM (McArdle et al., 1999). Waglerin-1 binds human receptors about 100-fold less tightly than mouse receptors (Molles et al., 2002). The manufacturer states that Syn-AKE blocks the same receptor reversibly; no peer-reviewed study has measured its receptor binding, end-plate effect or skin penetration. Independent work is limited to docking against MMPs and SIRT1 and a DPPH antioxidant assay (Gok et al., 2024). ### Evidence Clinical: at least one published human trial or an approved drug - Randomized, double-blind, placebo-controlled trial in 57 adults aged 50 to 65: 4% of a trade product (2500 ppm compound) twice daily for 4 weeks reduced forehead wrinkle area and length when frowning versus placebo, p<0.05 (Campiche et al., 2021) - Concentration-dependent DPPH radical scavenging; no cytotoxicity (MTT) or mutagenicity (Ames) at the tested doses; docking predicts MMP-13 and SIRT1 binding (Gok et al., 2024) - A serum combining the compound with acetyl hexapeptide-8, gluconolactone and niacinamide improved static and dynamic wrinkles over 12 weeks in two studies (n=50, n=42) with no control arm stated in the abstract (Zhu et al., 2026) - Parent toxin waglerin-1 selectively blocks the adult mouse muscle nicotinic receptor (McArdle et al., 1999) - Human-trial status: one published RCT of the compound alone (n=57, 4 weeks), run by the manufacturer; other human data use combination serums ### References - [Facial Expression Wrinkles and Their Relaxation by a Synthetic Peptide. Campiche R, Pascucci F, Jiang L, Vergne T, et al., International Journal of Peptide Research and Therapeutics, 2021](https://doi.org/10.1007/s10989-020-10146-z) - [Anti-aging activity of Syn-Ake peptide by in silico approaches and in vitro tests. Gok B, Budama-Kilinc Y, Kecel-Gunduz S, Journal of biomolecular structure & dynamics, 2024](https://doi.org/10.1080/07391102.2023.2223681) - [The effect of a serum containing acetyl hexapeptide-8, dipeptide diaminobutyroyl benzylamide diacetate and gluconolactone on skin biomarkers, wrinkles and skin texture: Ex vivo and clinical studies. Zhu M, He X, Zhu Z, Lynch S, et al., International journal of cosmetic science, 2026](https://doi.org/10.1111/ics.70087) - [Viper Venom Botox: The Molecular Origin and Evolution of the Waglerin Peptides Used in Anti-Wrinkle Skin Cream. Debono J, Xie B, Violette A, Fourmy R, et al., Journal of molecular evolution, 2017](https://doi.org/10.1007/s00239-016-9764-6) - [Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor. McArdle JJ, Lentz TL, Witzemann V, Schwarz H, et al., The Journal of pharmacology and experimental therapeutics, 1999](https://pubmed.ncbi.nlm.nih.gov/10087048/) - [Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors. Molles BE, Rezai P, Kline EF, McArdle JJ, et al., The Journal of biological chemistry, 2002](https://doi.org/10.1074/jbc.M109232200) - [Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Errante F, Ledwoń P, Latajka R, Rovero P, et al., Frontiers in chemistry, 2020](https://doi.org/10.3389/fchem.2020.572923) - [INDIVIDUAL ARTICLE: Real-World Clinical Experience With a Neuro-Peptide Serum in Combination With Botulinum Toxin Type-A Injections. Lupin M, Bjerring P, Andriessen A, Chantrey J, et al., Journal of drugs in dermatology : JDD, 2024](https://pubmed.ncbi.nlm.nih.gov/39496132/) ### Side effects No cytotoxicity or mutagenicity at the tested doses in vitro (Gok et al., 2024). The parent toxin waglerin-1 is lethal to adult mice through neuromuscular block (McArdle et al., 1999); the topical mimetic has no published systemic exposure or toxicity data in animals or people. Tolerability results from the RCT are not given in its abstract. Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured; no published skin-penetration data. Reaching the muscle receptor is unproven - Molecular weight: 375.47 Da - Sequence: [beta-Ala]-Pro-[Dab]-[NH-benzyl] ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Syn-Coll (Palmitoyl Tripeptide-5) URL: https://peptidelabs.app/peptides/syn-coll-palmitoyl-tripeptide-5/ Also known as: Palmitoyl Tripeptide-5, SYN-COLL, Pal-Lys-Val-Lys, Pal-KVK Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Palmitoylated tripeptide (Pal-Lys-Val-Lys) sold as Syn-Coll and marketed as a thrombospondin-1 mimic; evidence is supplier data and multi-ingredient products, with no single-ingredient trial. Palmitoyl tripeptide-5 is Pal-Lys-Val-Lys, sold by DSM (originally Pentapharm) as Syn-Coll. A 2021 review of cosmetic peptides found that the evidence for it sits mostly in patents and supplier brochures rather than controlled studies (Resende et al., 2021). Published human data come from products that combine it with other actives: a 12-week uncontrolled microneedle patch study (Avcil et al., 2020) and a 28-day study of lactoferrin and recombinant-collagen nanoparticles carrying it (Chen et al., 2025). In a Franz-cell test almost none of it crossed the skin from a hydrogel (Shariati Pour et al., 2023). The old '350% increase in collagen synthesis' and '84 days' figures have no published source. ### Benefits Collagen stimulation and MMP inhibition (supplier data and patents only), wrinkle and firmness changes from multi-ingredient products (human, uncontrolled) ### Dosing reference - Research dose: Topical; no published concentration for the single ingredient. Topical only. No published study states a concentration of palmitoyl tripeptide-5 on its own; the human studies used it inside microneedle patches or nanoparticle carriers with other actives. ### Mechanism Proposed by the manufacturer, with no direct test published. The claim rests on thrombospondin-1, which activates latent TGF-beta through its KRFK sequence binding the latency-associated peptide (Ribeiro et al., 1999). A related lipopeptide, elaidyl-KFK, activated latent TGF-beta in human dermal fibroblasts and raised collagen output, while the variant KQK was inactive (Cauchard et al., 2004). KVK, the sequence in Syn-Coll, was not tested there, and no peer-reviewed study has measured TGF-beta activation, collagen synthesis or MMP inhibition by palmitoyl tripeptide-5 itself (Resende et al., 2021). ### Evidence Preclinical: animal or in vitro data only - Microneedle patch combining palmitoyl tripeptide-5, acetyl octapeptide-3 and other actives: 25.8% fewer fine lines and 14.2% higher dermal density at 12 weeks, uncontrolled (Avcil et al., 2020) - Lactoferrin and recombinant-collagen nanoparticles carrying the peptide: 12.53% firmness gain and reduced nasolabial wrinkles at 28 days; no control arm described in the abstract (Chen et al., 2025) - Almost no transdermal permeation from a supramolecular hydrogel in Franz diffusion cells (Shariati Pour et al., 2023) - Review of cosmetics for sensitive skin: supporting data are mostly patents and supplier brochures (Resende et al., 2021) - Human-trial status: no published trial of palmitoyl tripeptide-5 alone; human data come from combination products ### References - [Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, et al., Pharmaceuticals (Basel, Switzerland), 2021](https://doi.org/10.3390/ph14080702) - [Delivery of Active Peptides by Self-Healing, Biocompatible and Supramolecular Hydrogels. Shariati Pour SR, Oddis S, Barbalinardo M, Ravarino P, et al., Molecules (Basel, Switzerland), 2023](https://doi.org/10.3390/molecules28062528) - [Efficacy of bioactive peptides loaded on hyaluronic acid microneedle patches: A monocentric clinical study. Avcil M, Akman G, Klokkers J, Jeong D, et al., Journal of cosmetic dermatology, 2020](https://doi.org/10.1111/jocd.13009) - [Supramolecular collagen nanoparticles for anti-wrinkle, skin whitening, and moisturizing effects. Chen W, Xiang N, Huang J, Xu H, et al., Colloids and surfaces. B, Biointerfaces, 2025](https://doi.org/10.1016/j.colsurfb.2024.114275) - [Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Errante F, Ledwoń P, Latajka R, Rovero P, et al., Frontiers in chemistry, 2020](https://doi.org/10.3389/fchem.2020.572923) - [Activation of latent transforming growth factor beta 1 and inhibition of matrix metalloprotease activity by a thrombospondin-like tripeptide linked to elaidic acid. Cauchard JH, Berton A, Godeau G, Hornebeck W, et al., Biochemical pharmacology, 2004](https://doi.org/10.1016/j.bcp.2004.01.028) - [The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta. Ribeiro SM, Poczatek M, Schultz-Cherry S, Villain M, et al., The Journal of biological chemistry, 1999](https://doi.org/10.1074/jbc.274.19.13586) ### Side effects No primary or cumulative skin reactions in the 12-week combination microneedle patch study (Avcil et al., 2020). No single-ingredient safety study has been published. Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Almost no transdermal permeation from a hydrogel in Franz cells (Shariati Pour et al., 2023); a nanoparticle carrier was reported to raise transdermal efficiency by 69.9% (Chen et al., 2025) - Molecular weight: 611.9 Da - Sequence: [Pal]-Lys-Val-Lys ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## TB-500 URL: https://peptidelabs.app/peptides/tb-500/ Also known as: Ac-LKKTETQ, Thymosin beta-4 fragment 17-23, TB 500, Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, 885340-08-9 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Acetylated heptapeptide Ac-LKKTETQ, the actin-binding region (residues 17 to 23) of thymosin beta-4 and not the full 43-residue protein; it promoted angiogenesis and wound repair in animal and cell models. TB-500 is the acetylated heptapeptide Ac-LKKTETQ. Analysis of commercial TB-500 identified this fragment, residues 17 to 23 of thymosin beta-4, not the full 43-residue protein (Esposito 2012), so most thymosin beta-4 literature describes a different molecule. The fragment carries the actin-binding motif: it matched the full protein for endothelial migration and aortic-arch sprouting at about 50 nM, and promoted dermal repair in aged mice as well as the protein did (Philp 2003a; Philp 2003b). A 2024 study found it broken down rapidly in serum and suggested the wound-healing activity belongs to the metabolite Ac-LKKTE (Rahaman 2024). The catalog lists this molecule again as TB-500 Fragment (17-23), id 68. FDA lists it in the withdrawn-nomination table of its 503A compounding safety-risk page, noting no human exposure data. ### Benefits Tissue repair, faster wound healing, tendon and ligament recovery, reduced inflammation, hair regrowth (animal models) ### Dosing reference - Research dose: 2 to 7.5 mg twice weekly: research-community range, no published human dose of the fragment. Horses received a single 10 mg dose in doping-detection work - Range: 2000 to 7500 mcg, 2x weekly (loading) - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg, 10 mg Subcutaneous or intramuscular in research use. The loading-then-maintenance schedule is community convention with no published basis; no human pharmacokinetic study of Ac-LKKTETQ exists. In rats the parent peptide cleared quickly, with Ac-LK the main early metabolite and Ac-LKK still detectable at 72 h (Rahaman 2024). ### Mechanism The LKKTETQ motif is the actin-binding site of thymosin beta-4 and carries much of its activity: peptides missing any part of the motif were inactive in endothelial migration and chick aortic-arch sprouting assays, while the heptapeptide matched the full protein at about 50 nM (Philp 2003a). Through G-actin binding it supports cytoskeletal remodeling and cell migration; in aged mice the same heptapeptide raised wound contracture and collagen deposition like the full protein (Philp 2003b). Other activities mapped to thymosin beta-4 sit outside this motif, including the N-terminal Ac-SDKP sequence that promotes cell survival (Sosne 2010), so they should not be assumed for the fragment. The ILK/PINCH/Akt survival pathway was shown for the full protein in cardiomyocytes (Bock-Marquette 2004), not for Ac-LKKTETQ. ### Evidence Preclinical: animal or in vitro data only - Chemical analysis of commercial TB-500 identified its active ingredient as the N-terminally acetylated 17-23 fragment of human thymosin beta-4, Ac-LKKTETQ (Esposito et al., 2012) - The seven-residue actin-binding motif was necessary and sufficient for the angiogenic activity of thymosin beta-4, matching the full protein at about 50 nM in endothelial migration and aortic-arch sprouting (Philp et al., 2003) - The synthetic LKKTETQ peptide promoted dermal wound repair in aged mice comparably to full-length thymosin beta-4 (Philp et al., 2003) - In rats and in vitro, Ac-LKKTETQ was rapidly metabolized; only the metabolite Ac-LKKTE showed significant wound-healing activity in fibroblasts, which the authors read as the parent being a prodrug (Rahaman et al., 2024) - Full-length thymosin beta-4, a different molecule, was well tolerated in a randomized placebo-controlled IV study in healthy volunteers at 42 to 1260 mg single and 14-day daily dosing (Ruff et al., 2010) - Human-trial status: no trial of Ac-LKKTETQ has been published. Published human data cover full-length thymosin beta-4 only (phase 1 IV, phase 2 dermal ulcer and ophthalmic trials). FDA notes no human exposure data for the LKKTETQ fragment ### References - [Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012](https://doi.org/10.1002/dta.1402) - [The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003](https://doi.org/10.1096/fj.03-0121fje) - [Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Philp D, Badamchian M, Scheremeta B, et al., Wound Repair and Regeneration, 2003](https://doi.org/10.1046/j.1524-475x.2003.11105.x) - [Biological activities of thymosin beta4 defined by active sites in short peptide sequences. Sosne G, Qiu P, Goldstein AL, Wheater M, FASEB Journal, 2010](https://doi.org/10.1096/fj.09-142307) - [Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. Rahaman KA, Muresan AR, Min H, et al., Journal of Chromatography B, 2024](https://doi.org/10.1016/j.jchromb.2024.124033) - [Doping control analysis of TB-500, a synthetic version of an active region of thymosin beta 4, in equine urine and plasma by liquid chromatography-mass spectrometry. Ho EN, Kwok WH, Lau MY, et al., Journal of Chromatography A, 2012](https://doi.org/10.1016/j.chroma.2012.09.043) - [A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ruff D, Crockford D, Girardi G, Zhang Y, Annals of the New York Academy of Sciences, 2010](https://doi.org/10.1111/j.1749-6632.2010.05474.x) - [Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D, Nature, 2004](https://doi.org/10.1038/nature03000) ### Side effects No human safety study of Ac-LKKTETQ has been published, and FDA states it has identified no human exposure data for this substance. Commonly reported by users: injection-site irritation, transient fatigue, a brief head rush after dosing. Full-length thymosin beta-4, a different molecule, was well tolerated IV at up to 1260 mg daily for 14 days in 40 healthy volunteers (Ruff 2010). Because the motif promotes angiogenesis and cell migration, use with active or suspected malignancy is theoretically inadvisable. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in any species. Rapidly metabolized in rat and human serum; metabolite Ac-LKK detectable in rat urine to 72 h (Rahaman 2024) - Molecular weight: 889.02 Da - Sequence: Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ, 7 aa; residues 17 to 23 of thymosin beta-4) ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [GHK-Cu](https://peptidelabs.app/peptides/ghk-cu/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## TB-500 Fragment (17-23) URL: https://peptidelabs.app/peptides/tb-500-fragment-17-23/ Also known as: TB4 fragment 17-23, Ac-LKKTETQ, LKKTETQ, Thymosin beta-4 actin-binding fragment, 885340-08-9 Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Ac-LKKTETQ, the actin-binding heptapeptide of Thymosin Beta-4, studied in animal models for cell migration, angiogenesis, wound healing and tissue repair. Ac-LKKTETQ, the acetylated actin-binding heptapeptide at residues 17 to 23 of thymosin beta-4. It is the same molecule as the catalog entry TB-500 (id 10): analysis of commercial TB-500 identified exactly this fragment (Esposito 2012), so this is a duplicate listing, not a distinct compound. The fragment carries the angiogenic activity of the parent protein. Peptides missing any part of the motif were inactive, while the heptapeptide matched the full protein at about 50 nM in endothelial migration and chick aortic-arch sprouting (Philp 2003a), and promoted dermal repair in aged mice as well as the protein did (Philp 2003b). Claims of better bioavailability than the full protein have no pharmacokinetic support; the one metabolism study found rapid degradation and suggested the metabolite Ac-LKKTE carries the activity (Rahaman 2024). ### Benefits Angiogenesis and endothelial migration matching full-length thymosin beta-4 at about 50 nM (in vitro and chick aortic arch); dermal wound repair in aged mice (animal). No human data ### Dosing reference - Research dose: 200 to 500 mcg daily: research-community range, no published human dose. The only published in-vivo dose is a single 10 mg administration in horses - Range: 200 to 500 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 5 mg Subcutaneous in research use. The improved-bioavailability claim has no supporting data: no pharmacokinetic study of this peptide exists in any species, and in rats it was rapidly metabolized (Rahaman 2024). Same molecule as the TB-500 catalog entry (id 10), so dosing conventions are identical. ### Mechanism LKKTETQ is the G-actin-binding motif of thymosin beta-4. Using natural protein, proteolytic fragments and synthetic peptides, the seven-residue motif was shown to be necessary and sufficient for angiogenic activity: migration of human umbilical vein endothelial cells and chick aortic-arch sprouting were near-identical between the protein and the peptide at about 50 nM, peptides lacking part of the motif were inactive, and soluble actin at 5 to 50 nM blocked the effect (Philp 2003a). Activities mapped elsewhere in the protein do not transfer: Ac-SDKP and the 15-residue N-terminal site govern cell survival and apoptosis, and the ILK/PINCH/Akt pathway was shown for full-length protein in cardiomyocytes (Sosne 2010; Bock-Marquette 2004). Better tissue penetration from the smaller size is a plausible idea with no published measurement. ### Evidence Preclinical: animal or in vitro data only - The seven-residue actin-binding motif was necessary and sufficient for the angiogenic activity of thymosin beta-4, matching the full protein at about 50 nM in endothelial migration and aortic-arch sprouting, with activity blocked by soluble actin (Philp et al., 2003) - The synthetic LKKTETQ peptide promoted dermal wound repair in aged mice comparably to full-length thymosin beta-4 (Philp et al., 2003) - Mass spectrometry of commercial TB-500 identified its active ingredient as this same N-terminally acetylated 17-23 fragment (Esposito et al., 2012) - A single 10 mg dose in horses was detectable as parent peptide and metabolites in plasma and urine, the only published in-vivo administration of this peptide (Ho et al., 2012) - In rats and in human serum the parent peptide was rapidly metabolized, with Ac-LK the main early metabolite and only Ac-LKKTE showing significant wound-healing activity in fibroblasts (Rahaman et al., 2024) - Human-trial status: none. No trial of Ac-LKKTETQ has been published, and FDA states it has identified no human exposure data for the LKKTETQ fragment ### References - [Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012](https://doi.org/10.1002/dta.1402) - [The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003](https://doi.org/10.1096/fj.03-0121fje) - [Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Philp D, Badamchian M, Scheremeta B, et al., Wound Repair and Regeneration, 2003](https://doi.org/10.1046/j.1524-475x.2003.11105.x) - [Biological activities of thymosin beta4 defined by active sites in short peptide sequences. Sosne G, Qiu P, Goldstein AL, Wheater M, FASEB Journal, 2010](https://doi.org/10.1096/fj.09-142307) - [Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. Rahaman KA, Muresan AR, Min H, et al., Journal of Chromatography B, 2024](https://doi.org/10.1016/j.jchromb.2024.124033) - [Doping control analysis of TB-500, a synthetic version of an active region of thymosin beta 4, in equine urine and plasma by liquid chromatography-mass spectrometry. Ho EN, Kwok WH, Lau MY, et al., Journal of Chromatography A, 2012](https://doi.org/10.1016/j.chroma.2012.09.043) - [A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ruff D, Crockford D, Girardi G, Zhang Y, Annals of the New York Academy of Sciences, 2010](https://doi.org/10.1111/j.1749-6632.2010.05474.x) - [Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D, Nature, 2004](https://doi.org/10.1038/nature03000) ### Side effects No human safety study of Ac-LKKTETQ has been published, and FDA states it has identified no human exposure data for this substance. Commonly reported by users: injection-site irritation and transient fatigue. Full-length thymosin beta-4, a different molecule, was well tolerated IV at up to 1260 mg daily for 14 days in 40 healthy volunteers (Ruff 2010). Because the motif promotes angiogenesis and cell migration, use with active or suspected malignancy is theoretically inadvisable. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured in any species. Rapidly metabolized in rat and human serum; metabolite Ac-LKK detectable in rat urine to 72 h (Rahaman 2024) - Molecular weight: 889.02 Da - Sequence: Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ, 7 aa; residues 17 to 23 of thymosin beta-4) ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## Tesamorelin URL: https://peptidelabs.app/peptides/tesamorelin/ Also known as: Egrifta, Egrifta SV, Egrifta WR, TH9507, TH-9507, Tesamorelin acetate Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic GHRH(1-44) analog, FDA-approved 2010 (Egrifta) for excess abdominal fat in HIV lipodystrophy; cut visceral fat about 15% vs placebo over 26 weeks in two phase 3 RCTs (n=806). Tesamorelin (TH9507) is human GHRH(1-44) with a trans-3-hexenoyl group on the N-terminal tyrosine that resists dipeptidyl peptidase cleavage. The FDA approved it on 10 Nov 2010 (Egrifta, Theratechnologies) to reduce excess abdominal fat in HIV-infected adults with lipodystrophy; it has no non-HIV indication. In the pooled phase 3 trials (n=806), 2 mg SC daily for 26 weeks reduced visceral adipose tissue by 15.4% relative to placebo, lowered triglycerides, and left abdominal subcutaneous fat unchanged; the loss reversed within 26 weeks of stopping (Falutz 2010). Smaller RCTs showed reductions in liver fat (Stanley 2014, n=50; Stanley 2019, n=61). A 20-week RCT in 152 older adults with and without mild cognitive impairment found improved executive function and verbal memory (Baker 2012). Current presentations are Egrifta SV (1.4 mg daily) and Egrifta WR (1.28 mg daily). ### Benefits Visceral fat reduction (human RCT, n=806), triglyceride and cholesterol/HDL improvement (human RCT), liver fat reduction (human RCT, n=50 and n=61), IGF-1 increase (human RCT), cognitive test gains in older adults and MCI (human RCT, n=152) ### Dosing reference - Research dose: 1.28-2 mg SC once daily per FDA labels (Egrifta 2 mg; Egrifta SV 1.4 mg; Egrifta WR 1.28 mg); phase 3 trials used 2 mg daily - Range: 1280 to 2000 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 2 mg, 5 mg Subcutaneous once daily (abdomen). Label contraindications: disruption of the hypothalamic-pituitary axis, active malignancy, pregnancy, hypersensitivity. Visceral fat loss reversed within 26 weeks of stopping in the phase 3 extension (Falutz 2010). Fasting glucose rose transiently at 2 weeks in one RCT (Stanley 2014). Reconstitution: Egrifta WR 11.6 mg vial in 1.3 mL bacteriostatic water (8 mg/mL). ### Mechanism Tesamorelin is GHRH(1-44) with an N-terminal trans-3-hexenoyl modification that slows dipeptidyl peptidase IV cleavage (Ferdinandi 2007). It binds the pituitary GHRH receptor and increases pulsatile GH secretion with preserved IGF-1 negative feedback; IGF-1 rose 81% over 26 weeks in the phase 3 trial (Falutz 2007). Visceral fat falls while abdominal subcutaneous fat does not, consistent with GH-driven lipolysis of visceral depots (Falutz 2010). Reductions in liver fat seen in two RCTs are proposed to follow the visceral fat change (Stanley 2014; Stanley 2019). ### Evidence Clinical: at least one published human trial or an approved drug - Phase 3 RCT, n=412: visceral fat -15.2% vs +5.0% placebo over 26 weeks; triglycerides -50 mg/dL; IGF-1 +81% (Falutz et al., 2007) - Pooled phase 3, n=806: VAT treatment effect -15.4%, abdominal SC fat unchanged, effect maintained to 52 weeks and lost after switching to placebo (Falutz et al., 2010) - RCT, n=50: VAT -34 cm2 and liver fat reduced over 6 months; transient fasting glucose rise at 2 weeks (Stanley et al., 2014) - RCT, n=61: reduced hepatic fat fraction and prevented fibrosis progression in HIV-associated NAFLD over 12 months (Stanley et al., 2019) - RCT, n=152: 20 weeks improved executive function and verbal memory in older adults with and without MCI (Baker et al., 2012) - Human-trial status: FDA-approved 10 Nov 2010 (Egrifta, NDA 022505) for excess abdominal fat in HIV lipodystrophy; Egrifta SV and WR presentations followed; not approved for any non-HIV indication ### References - [Metabolic effects of a growth hormone-releasing factor in patients with HIV. Falutz J, Allas S, Blot K, et al., New England Journal of Medicine, 2007](https://doi.org/10.1056/NEJMoa072375) - [Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. Falutz J, Mamputu JC, Potvin D, et al., Journal of Clinical Endocrinology & Metabolism, 2010](https://doi.org/10.1210/jc.2010-0490) - [Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. Falutz J, Potvin D, Mamputu JC, et al., Journal of Acquired Immune Deficiency Syndromes, 2010](https://doi.org/10.1097/QAI.0b013e3181cbdaff) - [Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. Stanley TL, Feldpausch MN, Oh J, et al., JAMA, 2014](https://doi.org/10.1001/jama.2014.8334) - [Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Stanley TL, Fourman LT, Feldpausch MN, et al., Lancet HIV, 2019](https://doi.org/10.1016/S2352-3018(19)30338-8) - [Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Baker LD, Barsness SM, Borson S, et al., Archives of Neurology, 2012](https://doi.org/10.1001/archneurol.2012.1970) - [Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Ferdinandi ES, Brazeau P, High K, Procter B, Fournier S, Abribat T, Basic & Clinical Pharmacology & Toxicology, 2007](https://doi.org/10.1111/j.1742-7843.2007.00008.x) ### Side effects Label (>5%): arthralgia, injection-site erythema and pruritus, pain in extremity, peripheral edema, myalgia. Phase 3 trials: adverse events did not differ from placebo overall but more tesamorelin patients withdrew for an adverse event (Falutz 2007); no clinically meaningful glucose change at 26 or 52 weeks in the pooled analysis (Falutz 2010), though one small RCT saw a transient fasting-glucose rise (Stanley 2014). Hypersensitivity reactions are listed on the label. ### Storage - Storage: 20-25C for Egrifta SV and WR vials (label); research-grade lyophilized vials are commonly refrigerated 2-8C (general guidance) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: Label: Egrifta SV is used immediately after reconstitution; Egrifta WR is discarded 7 days after mixing (20-25C). 28-30 days refrigerated is general peptide guidance, not label ### Pharmacology - Half-life: ~8-11 min (human, SC; current Egrifta SV and WR labels) - Bioavailability: <4% absolute (human, SC 2 mg; FDA label) - Molecular weight: 5135.89 Da - Sequence: [trans-3-hexenoyl]YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL[NH2] ### Stacks with - [Ipamorelin](https://peptidelabs.app/peptides/ipamorelin/) - [CJC-1295](https://peptidelabs.app/peptides/cjc-1295/) ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) ## Tesamorelin + Ipamorelin Blend URL: https://peptidelabs.app/peptides/tesamorelin-ipamorelin-blend/ Also known as: Tesa/Ipa, Visceral Fat Blend, Premium GH Stack Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vial blend of tesamorelin and ipamorelin (vendors sell 6/2 mg and 10/3 mg); tesamorelin cut visceral fat in HIV phase 3 trials, and no study has tested the pair. Tesamorelin is approved by FDA as Egrifta (2010) for excess abdominal fat in HIV lipodystrophy; this research blend is not that product. Vendors mix tesamorelin and ipamorelin at about 3:1, as 8 mg (6/2 mg) or 13 mg (10/3 mg) vials. In two phase 3 RCTs (n=806), tesamorelin 2 mg daily cut visceral fat about 15% versus placebo over 26 weeks, and the effect was lost after stopping (Falutz 2010). Ipamorelin has one human PK study and one negative phase 2 trial in postoperative ileus (Beck 2014). GHRH-class and GHRP-class peptides were synergistic for GH release in men (Bowers 1990), the rationale for the pairing, but no study has tested tesamorelin with ipamorelin, and the trial results apply to tesamorelin alone in HIV. FDA lists ipamorelin in category 2 for 503B outsourcing on its compounding safety-risk page. ### Benefits Visceral fat reduction (human RCTs, tesamorelin in HIV lipodystrophy); GH pulse after IV ipamorelin (human PK study); combined effect untested. No data for the blend ### Dosing reference - Research dose: 1 to 2 mg of blend daily (about 0.75 to 1.5 mg tesamorelin and 0.25 to 0.5 mg ipamorelin at the 6/2 mg ratio): vendor/community range, no published human dose of the blend. The approved tesamorelin product is labelled at 1.28 to 2 mg daily - Range: 1000 to 2000 mcg, 1x daily before bed - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 8 mg, 13 mg Subcutaneous once daily in community use, often at bedtime. Egrifta labels give tesamorelin 1.28 to 2 mg SC once daily depending on presentation, and the phase 3 trials used 2 mg daily; those doses apply to the approved product, not this blend. Visceral fat returned after tesamorelin was stopped (Falutz 2010). Human ipamorelin doses were IV (0.03 mg/kg twice daily in the ileus trial). ### Mechanism Proposed, from component and class studies. Tesamorelin is GHRH(1-44) with a trans-3-hexenoic acid group on its N-terminus that resists breakdown; it acts on the pituitary GHRH receptor and raised IGF-1 81% in a phase 3 trial (Falutz 2007). Its visceral-fat effect is attributed to the GH rise. Ipamorelin is a ghrelin-receptor agonist that released GH without raising ACTH or cortisol in swine (Raun 1998). GHRH-receptor and ghrelin-receptor agonists given together raise GH more than either alone in men (Bowers 1990), shown with other analogs. Whether adding ipamorelin changes tesamorelin's visceral-fat or glucose effects has not been studied. ### Evidence Preclinical: animal or in vitro data only - Phase 3 RCT, n=412: tesamorelin 2 mg daily cut visceral fat 15.2% vs a 5.0% rise on placebo over 26 weeks in HIV lipodystrophy (Falutz et al., 2007) - Pooled phase 3, n=806: visceral fat treatment effect -15.4%, kept to 52 weeks and lost after switching to placebo (Falutz et al., 2010) - RCT, n=50: tesamorelin reduced visceral and liver fat over 6 months, with a transient fasting glucose rise at 2 weeks (Stanley et al., 2014) - Phase 2 RCT of IV ipamorelin in postoperative ileus (n=114): well tolerated, no efficacy difference from placebo (Beck et al., 2014) - Human-trial status: no study has tested the blend as sold. Tesamorelin was approved in 2010 (Egrifta) for HIV-associated abdominal fat only; ipamorelin's only RCT was negative, and GHRH plus GHRP synergy in men was shown with other analogs (Bowers et al., 1990) ### References - [Metabolic effects of a growth hormone-releasing factor in patients with HIV. Falutz J, Allas S, Blot K, et al., New England Journal of Medicine, 2007](https://doi.org/10.1056/NEJMoa072375) - [Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. Falutz J, Mamputu JC, Potvin D, et al., Journal of Clinical Endocrinology & Metabolism, 2010](https://doi.org/10.1210/jc.2010-0490) - [Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. Stanley TL, Feldpausch MN, Oh J, et al., JAMA, 2014](https://doi.org/10.1001/jama.2014.8334) - [Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998](https://doi.org/10.1530/eje.0.1390552) - [Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999](https://doi.org/10.1023/a:1018955126402) - [Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014](https://doi.org/10.1007/s00384-014-2030-8) - [Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990](https://doi.org/10.1210/jcem-70-4-975) ### Side effects No human safety study of the blend has been published. On the Egrifta labels the most common tesamorelin adverse reactions (over 5%) were joint pain, injection-site redness and itching, pain in the limbs, peripheral edema and muscle pain; one small RCT saw a transient fasting-glucose rise (Stanley 2014). IV ipamorelin was well tolerated in a phase 2 trial (Beck 2014). Label contraindications for tesamorelin include active malignancy, disruption of the hypothalamic-pituitary axis and pregnancy. Ipamorelin is in category 2 of FDA's 503B interim policy (added 2023-09-29) and in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Tesamorelin ~8 to 11 min (human, SC; current Egrifta SV and WR labels). Ipamorelin ~2 h terminal (human, IV) - Bioavailability: Tesamorelin SC under 4% (human; Egrifta SV label). Ipamorelin human data are IV. No data for the blend ### Categories - [Growth Hormone](https://peptidelabs.app/peptides/category/growth-hormone/) - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Blend](https://peptidelabs.app/peptides/category/blend/) ## Tesofensine URL: https://peptidelabs.app/peptides/tesofensine/ Also known as: NS-2330, NS2330, NS 2330 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Small-molecule triple monoamine reuptake inhibitor, not a peptide. In a 24-week phase 2 trial (n=203), 0.5 mg daily gave 9.2% weight loss versus 2.0% with placebo plus diet. Tesofensine (NS2330) was developed by NeuroSearch for Parkinson's and Alzheimer's disease, where effects were modest; a pooled analysis of four 14-week trials (n=968) found dose-related weight loss (Astrup 2008, Obesity). In a Danish phase 2 obesity trial (n=203), 0.25, 0.5 and 1.0 mg daily with diet gave 4.5%, 9.2% and 10.6% weight loss over 24 weeks versus 2.0% with placebo (Astrup 2008). The Lancet issued an expression of concern in 2013 over under-reported adverse events, and the authors published a correction (Astrup 2013). Mechanism studies showed raised satiety, lower appetite and higher fat oxidation (Sjödin 2010; Gilbert 2012). A Mexican phase 3 trial (n=372) was reported by press release in 2018 but not in a peer-reviewed journal (Chakhtoura 2023). Combined with metoprolol (Tesomet) it was tested in hypothalamic obesity (Huynh 2022). No FDA or EMA approval. ### Benefits Weight loss (human RCT, 24 weeks), increased satiety and reduced appetite (human RCT), higher 24-hour fat oxidation (human, 2 weeks) ### Dosing reference - Research dose: 0.25 to 0.5 mg once daily by mouth (phase 2 and phase 3 obesity doses; 1.0 mg was also tested) - Range: 250 to 500 mcg, 1x daily Oral, once daily. The phase 2 obesity trial tested 0.25, 0.5 and 1.0 mg for 24 weeks with an energy-restricted diet (Astrup 2008); the Mexican phase 3 used 0.25 and 0.5 mg. The Tesomet combination used 0.5 mg with metoprolol 50 mg (Huynh 2022). With a half-life near 10 days, steady state takes weeks. ### Mechanism Tesofensine inhibits presynaptic reuptake of noradrenaline, dopamine and serotonin. In overweight men it raised satiety and fullness, lowered prospective food intake, raised 24-hour fat oxidation by 18 g and raised night-time energy expenditure 4.6%, so appetite suppression is the main driver of weight loss with a small energy-expenditure component (Sjödin 2010). Appetite effects were dose-dependent over 24 weeks (Gilbert 2012). Its major metabolite M1 circulates even longer (Lehr 2007). Hypothalamic and dopamine-reward pathways are proposed from rodent work. ### Evidence Clinical: at least one published human trial or an approved drug - 24-week phase 2 trial (n=203): 4.5%, 9.2% and 10.6% weight loss at 0.25, 0.5 and 1.0 mg versus 2.0% with placebo plus diet; heart rate rose 7.4 bpm at 0.5 mg (Astrup et al., 2008) - The Lancet placed an expression of concern on the 2008 trial in 2013 for under-reported adverse events; the authors published the missing data (Astrup et al., 2013) - 2 weeks of treatment raised satiety and 24-hour fat oxidation and gave 1.8 kg weight loss over placebo in overweight men (Sjödin et al., 2010) - Tesofensine 0.5 mg with metoprolol 50 mg gave 6.3% additional weight loss over placebo in 21 adults with hypothalamic obesity (Huynh et al., 2022) - Human-trial status: phase 3 in Mexico (n=372) reported only by press release (Chakhtoura et al., 2023); Parkinson's and Alzheimer's programmes not pursued; not approved by FDA or EMA ### References - [Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Astrup A, Madsbad S, Breum L, et al., Lancet, 2008](https://doi.org/10.1016/S0140-6736(08)61525-1) - [Under-reporting of adverse effects of tesofensine. Astrup A, Madsbad S, Breum L, et al., Lancet, 2013](https://doi.org/10.1016/S0140-6736(13)61563-9) - [Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease. Astrup A, Meier DH, Mikkelsen BO, et al., Obesity, 2008](https://doi.org/10.1038/oby.2008.56) - [The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Sjödin A, Gasteyger C, Nielsen AL, et al., International Journal of Obesity, 2010](https://doi.org/10.1038/ijo.2010.87) - [The effect of tesofensine on appetite sensations. Gilbert JA, Gasteyger C, Raben A, et al., Obesity, 2012](https://doi.org/10.1038/oby.2011.197) - [Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease. Lehr T, Staab A, Tillmann C, et al., British Journal of Clinical Pharmacology, 2007](https://doi.org/10.1111/j.1365-2125.2007.02855.x) - [Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity. Huynh K, Klose M, Krogsgaard K, et al., European Journal of Endocrinology, 2022](https://doi.org/10.1530/EJE-21-0972) - [Pharmacotherapy of obesity: an update on the available medications and drugs under investigation. Chakhtoura M, Haber R, Ghezzawi M, et al., EClinicalMedicine, 2023](https://doi.org/10.1016/j.eclinm.2023.101882) ### Side effects In the 24-week phase 2 trial the most common effects were dry mouth, nausea, constipation, hard stools, diarrhoea and insomnia; heart rate rose 7.4 bpm at 0.5 mg, while blood pressure did not rise significantly at 0.25 or 0.5 mg (Astrup 2008). Adverse events in that trial were later found under-reported (Astrup 2013). With metoprolol, sleep disturbance, dry mouth and headache were common and one case of worsened anxiety led to withdrawal (Huynh 2022). It is cleared by CYP3A4; itraconazole raised exposure in a PK study. Mood effects, irritability and stimulant-like effects are commonly reported (anecdotal). ### Storage - Storage: Room temperature, dry (general small-molecule guidance; no compound-specific CoA located) - Lyophilized: 12+ months ### Pharmacology - Half-life: ~234 h, with active metabolite M1 ~374 h (oral, population PK in Alzheimer's patients; Lehr 2007) - Bioavailability: Oral; absolute bioavailability not located in published sources. Long half-life supports once-daily dosing (Lehr 2007) - Molecular weight: 328.3 Da ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Testagen URL: https://peptidelabs.app/peptides/testagen/ Also known as: KEDG, Lys-Glu-Asp-Gly Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tetrapeptide KEDG (Lys-Glu-Asp-Gly), described as pituitary-derived; studied for thyroid and thymus effects in hypophysectomized chickens. No testis study exists. The name Testagen implies a testicular peptide, but no published study tested KEDG on the testis, sperm or testosterone. The developer group's 2022 table lists Testagen as KEDG (Lys-Glu-Asp-Gly) (Khavinson 2022); the old record stored KED, which is Vesugen. All animal work treats KEDG as a pituitary-derived peptide and comes from one group: in neonatally hypophysectomized chickens and old hens it was compared with AEDG (Epitalon) for effects on thyroid structure and hormonal activity, immunity, hemostasis and thymus morphology (Kuznik 2008, 2010, 2011; Pateyk 2013). Cell work showed short fluorescence-labelled peptides entering HeLa cell nuclei (Fedoreyeva 2011). No human trial has been published. ### Benefits Thyroid structure and hormonal activity in hypophysectomized chickens and old hens (avian), thymus morphology in hypophysectomized birds (avian), nuclear entry and DNA binding of short peptides (in vitro) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. No published human dose or schedule; the bird studies are not a basis for one. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Proposed by the developing group and never tested on reproductive tissue. Short fluorescence-labelled peptides of this series entered HeLa cell nuclei and bound DNA oligonucleotides in vitro (Fedoreyeva 2011), which the group reads as support for gene regulation by direct DNA binding (Khavinson 2020). Docking predicts uptake through PEPT and LAT family transporters (Khavinson 2022, 2023). The Leydig cell, steroidogenesis and HPG-axis claims in the old text had no source and were removed. ### Evidence Preclinical: animal or in vitro data only - In neonatally hypophysectomized chickens, KEDG and AEDG were tested for effects on thyroid structure and function (Kuznik et al., 2008) - In hypophysectomized young chickens and old hens, both peptides were studied for thyroid hormonal activity and structure, immunity and hemostasis (Kuznik et al., 2010, 2011) - Thymus morphology was examined in hypophysectomized young and old birds given KEDG or AEDG (Pateyk et al., 2013) - Short fluorescence-labelled peptides entered HeLa cell nuclei and bound DNA oligonucleotides in vitro (Fedoreyeva et al., 2011) - Human-trial status: none published. No study in any species tested testis, sperm or testosterone, and nearly all work comes from one group ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Effect of tetrapeptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the structure and function of the thyroid gland in neonatally hypophysectomized chickens. Kuznik BI, Pateyuk AV, Rusaeva NS, Bulletin of Experimental Biology and Medicine, 2008](https://doi.org/10.1007/s10517-008-0033-6) - [Effects of hypophyseal Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthetic peptides on immunity, hemostasis, morphology and functions of the thyroid gland in neonatally hypophysectomized chicken and one-year-old birds (in Russian). Kuznik BI, Pateiuk AV, Rusaeva NS, Baranchugova LM, et al., Patologicheskaia Fiziologiia i Eksperimental'naia Terapiia, 2010](https://pubmed.ncbi.nlm.nih.gov/20731122/) - [Effects of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on hormonal activity and structure of the thyroid gland in hypophysectomized young chickens and old hens. Kuznik BI, Pateyuk AV, Rusaeva NS, Baranchugova LM, et al., Bulletin of Experimental Biology and Medicine, 2011](https://doi.org/10.1007/s10517-011-1177-3) - [Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds. Pateyk AV, Baranchugova LM, Rusaeva NS, Obydenko VI, et al., Bulletin of Experimental Biology and Medicine, 2013](https://doi.org/10.1007/s10517-013-2029-0) - [Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Fedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF, Biochemistry (Moscow), 2011](https://doi.org/10.1134/S0006297911110022) - [Peptide Regulation of Cell Differentiation. Khavinson V, Linkova N, Diatlova A, Trofimova S, Stem Cell Reviews and Reports, 2020](https://doi.org/10.1007/s12015-019-09938-8) - [Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters. Khavinson VK, Linkova NS, Rudskoy AI, Petukhov MG, Biomolecules, 2023](https://doi.org/10.3390/biom13030552) ### Side effects No controlled safety study has been published in any species; the bird and cell studies, all from the developing group, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species. Docking predicts transport by PEPT and LAT family carriers (Khavinson 2022, 2023) - Molecular weight: 447.44 Da - Sequence: KEDG (Lys-Glu-Asp-Gly) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) ## Thymagen URL: https://peptidelabs.app/peptides/thymagen/ Also known as: Timogen, Thymogen, IM862, Oglufanide, EW dipeptide, Glu-Trp Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic dipeptide EW (Glu-Trp), registered in Russia as Timogen; tested in the US as IM862 (oglufanide), where a phase III trial in AIDS-related Kaposi sarcoma found no benefit over placebo. Thymagen is the dipeptide Glu-Trp, the active substance of Timogen, a drug registered in Russia (ЛП-№(001808)-(РГ-RU), 13 February 2023) as a 100 mcg/1 mL intramuscular injection, a 25 mcg per dose nasal spray and a 0.05% cream. The same molecule was developed in the US as IM862, later named oglufanide, an angiogenesis inhibitor. A randomized study in AIDS-related Kaposi sarcoma (n=44) was followed by a phase III trial (n=202) in which it was not superior to placebo (Tulpule 2000; Noy 2005). Phase II work in renal cell carcinoma and prostate cancer also failed (Deplanque 2004; Mao 2007). In rats it slowed aging and inhibited spontaneous carcinogenesis (Anisimov 2000). Most Russian work comes from the developing group. ### Benefits Registered drug in Russia (Timogen: injection, nasal spray, cream), AIDS-related Kaposi sarcoma: not superior to placebo (human phase III RCT, n=202), slower aging and fewer spontaneous tumours (rat), NK-cell-dependent antitumour activity (animal) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, 2 to 10 times the Russian label dose of 100 mcg IM - Range: 200 to 1000 mcg, 1x daily Russian label (Timogen): 100 mcg in 1 mL by intramuscular injection, a 25 mcg per dose intranasal spray and a 0.05% cream. IM862 was given as a nasal solution in the US Kaposi sarcoma trials (Tulpule 2000). The catalog range of 200 to 1000 mcg daily is a community figure, 2 to 10 times the label injection dose. ### Mechanism Proposed, from mixed sources. Under the name IM862 it was developed as an angiogenesis inhibitor (Noy 2005). Its antitumour activity in vivo required natural killer cell cytolytic activity (Smith 2003). The developer group reports that EW, as a component of Thymalin, alters genes and proteins involved in COVID-19 pathogenesis (Linkova 2023). The Russian label states the dipeptide is cleaved to glutamic acid and tryptophan. The old claims about thymocyte selection and T-cell export had no source. ### Evidence Clinical: at least one published human trial or an approved drug - Randomized study of IM862 nasal solution in AIDS-related Kaposi sarcoma, n=44 (Tulpule et al., 2000) - Slowed aging and inhibited spontaneous carcinogenesis in rats (Anisimov et al., 2000) - Antitumour activity in vivo depended on natural killer cell cytolytic activity (Smith et al., 2003) - In human peripheral blood lymphocyte culture, a chromosome aberration study found high concentrations reduced lymphocyte proliferation (Rushkovskii et al., 1996) - Phase II trials: no responses in metastatic renal cell carcinoma (Deplanque et al., 2004); failed as a candidate in an intermittent androgen ablation prostate cancer screen (Mao et al., 2007) - Human-trial status: registered in Russia as Timogen. As IM862 it was not superior to placebo in a phase III RCT in AIDS-related Kaposi sarcoma (n=202; response rate 23% with IM862 vs 21% with placebo) and time to progression was shorter on IM862 (16 vs 35 weeks) (Noy et al., 2005) ### References - [Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: from the AIDS Malignancy Consortium and IM862 Study Team. Noy A, Scadden DT, Lee J, Dezube BJ, et al., Journal of Clinical Oncology, 2005](https://doi.org/10.1200/JCO.2005.11.043) - [Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma. Tulpule A, Scadden DT, Espina BM, Cabriales S, et al., Journal of Clinical Oncology, 2000](https://doi.org/10.1200/JCO.2000.18.4.716) - [Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma. Deplanque G, Madhusudan S, Jones PH, Wellmann S, et al., British Journal of Cancer, 2004](https://doi.org/10.1038/sj.bjc.6602126) - [Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies. Mao S, Daliani DD, Wang X, Thall PF, et al., The Prostate, 2007](https://doi.org/10.1002/pros.20649) - [Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Anisimov VN, Khavinson VK, Morozov VG, Biogerontology, 2000](https://doi.org/10.1023/a:1010042008969) - [Natural killer cell cytolytic activity is necessary for in vivo antitumor activity of the dipeptide L-glutamyl-L-tryptophan. Smith DL, Cai J, Zhu S, Wei W, et al., International Journal of Cancer, 2003](https://doi.org/10.1002/ijc.11253) - [The Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19. Linkova N, Khavinson V, Diatlova A, Petukhov M, et al., International Journal of Molecular Sciences, 2023](https://doi.org/10.3390/ijms241713377) - [The effect of thymogen on the chromosome aberration level in a culture of human peripheral blood lymphocytes (in Russian). Rushkovskiĭ SR, Chegrinets SE, Bezrukov VF, Khrapunov SN, Tsitologiia i Genetika, 1996](https://pubmed.ncbi.nlm.nih.gov/9026996/) ### Side effects In human lymphocyte culture, high concentrations reduced proliferation, measured in a chromosome aberration study (Rushkovskii 1996). No adverse-event summary from the IM862 trials or the Russian label is included yet. Commonly reported (anecdotal): injection-site irritation. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published half-life found. The Russian label states the dipeptide is cleaved to glutamic acid and tryptophan - Bioavailability: Not reported in the sources reviewed. Registered routes in Russia are intramuscular, intranasal and topical; IM862 was given as a nasal solution in US trials (Tulpule 2000) - Molecular weight: 333.34 Da - Sequence: Glu-Trp ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Immune](https://peptidelabs.app/peptides/category/immune/) ## Thymalin URL: https://peptidelabs.app/peptides/thymalin/ Also known as: Thymic extract, Thymus extract Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Peptide extract of calf thymus, registered in Russia as a 10 mg injectable lyophilizate; its developers tested it as add-on therapy for COVID-19 in an open-label randomized trial (n=92). Thymalin is a complex of peptides extracted from calf thymus, registered in Russia (ЛП-№(005867)-(РГ-RU), 21 June 2024) as a 10 mg lyophilizate for intramuscular injection. It is not a single synthetic peptide; its developers report the dipeptides KE (Vilon) and EW (Thymagen) in its composition (Linkova 2023). The strongest human study is an open-label randomized trial in COVID-19, 42 treated vs 50 controls, 10 mg IM daily for 5 days, run by the developer group (Khavinson 2021). An older report from the same group described longer survival in elderly people given thymus and pineal peptides, with a weak design (Khavinson 2003). T-activin is a different thymus product. ### Benefits Registered drug in Russia (intramuscular lyophilizate), add-on therapy in COVID-19 (human open-label RCT, n=92, developer group), longer survival in older adults (human, weak design, developer group), hematopoietic stem cell differentiation (human cells) ### Dosing reference - Research dose: 5 to 20 mg IM daily for 3 to 10 days (Russian label, adults) - Range: 5000 to 20000 mcg, 1x daily - Common vial sizes: 10 mg Intramuscular only. Russian label: 10 mg lyophilizate per vial; adults 5 to 20 mg daily for 3 to 10 days. The COVID-19 trial used 10 mg IM daily for 5 days (Khavinson 2021). No oral form is registered. ### Mechanism Proposed. As a mixture its action has not been tied to one molecule. The developers report that it activates differentiation of human hematopoietic stem cells (Khavinson 2020). They identify the dipeptides KE and EW in the drug and report that both alter expression of genes and proteins involved in COVID-19 pathogenesis (Linkova 2023). A 1997 review from the same group places it among natural and synthetic thymic peptides for immune dysfunction (Morozov 1997). Restoration of the thymic microenvironment is a hypothesis, not a measured effect. ### Evidence Clinical: at least one published human trial or an approved drug - Open-label randomized trial in COVID-19: 42 patients given 10 mg IM daily for 5 days within complex therapy vs 50 controls, run by the developer group (Khavinson et al., 2021) - Activated differentiation of human hematopoietic stem cells (Khavinson et al., 2020) - The dipeptides KE and EW, identified in the drug, altered expression of genes and proteins linked to COVID-19 pathogenesis (Linkova et al., 2023) - Older adults given thymus and pineal peptide courses had longer survival in a weakly designed report from the developer group (Khavinson and Morozov, 2003) - Human-trial status: registered drug in Russia (label: adults 5 to 20 mg IM daily for 3 to 10 days); one open-label developer-run RCT; no independent trial ### References - [Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19. Khavinson VK, Kuznik BI, Trofimova SV, Volchkov VA, et al., Stem Cell Reviews and Reports, 2021](https://doi.org/10.1007/s12015-020-10087-6) - [Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Khavinson VK, Linkova NS, Kvetnoy IM, Polyakova VO, et al., Bulletin of Experimental Biology and Medicine, 2020](https://doi.org/10.1007/s10517-020-05016-z) - [The Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19. Linkova N, Khavinson V, Diatlova A, Petukhov M, et al., International Journal of Molecular Sciences, 2023](https://doi.org/10.3390/ijms241713377) - [Peptides of pineal gland and thymus prolong human life. Khavinson VKh, Morozov VG, Neuro Endocrinology Letters, 2003](https://pubmed.ncbi.nlm.nih.gov/14523363/) - [Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Morozov VG, Khavinson VK, International Journal of Immunopharmacology, 1997](https://doi.org/10.1016/s0192-0561(97)00058-1) ### Side effects No independent safety study has been published; the developer-run trial and survival report were not designed as safety studies. Commonly reported (anecdotal): injection-site pain and transient local reactions. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data; a mixture of peptides - Bioavailability: Given by intramuscular injection only (Russian label); no published pharmacokinetic data ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Immune](https://peptidelabs.app/peptides/category/immune/) ## Thymosin Alpha-1 URL: https://peptidelabs.app/peptides/thymosin-alpha-1/ Also known as: Zadaxin, Thymalfasin, Tα1, TA1 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview 28-residue thymic peptide (thymalfasin, Zadaxin) approved in over 30 countries for hepatitis B and C and as an immune adjuvant, with no US application on file; acts as an immune response modifier. Thymosin alpha-1 is a 28-residue thymic peptide; its synthetic form, thymalfasin, is sold as Zadaxin. It is approved in more than 30 countries for chronic hepatitis B and C and as an immune adjuvant, with approvals granted market by market from the late 1990s (Tuthill, 2007; Goldstein and Goldstein, 2009). It has no US marketing approval: a Drugs@FDA query for thymalfasin and for Zadaxin returns no application. Randomised trials in hepatitis B gave mixed results, positive in one 98-patient trial (Chien et al., 1998) and null in a 97-patient placebo-controlled phase 3 (Mutchnick et al., 1999). In sepsis, a 361-patient single-blind trial suggested lower 28-day mortality (Wu et al., 2013) but the 1106-patient double-blind phase 3 found none (Wu et al., 2025). ### Benefits Immune support, antiviral, vaccine enhancement, T-cell activation ### Dosing reference - Research dose: 1.6 mg subcutaneously twice weekly (the hepatitis B trial regimen and the marketed vial size) - Range: 1600 to 3200 mcg, 2-3x weekly - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 1.6 mg, 5 mg Subcutaneous injection. Hepatitis B trials used 1.6 mg twice weekly for 26 to 52 weeks (Chien et al., 1998; Mutchnick et al., 1999). The melanoma trial tested 1.6, 3.2 and 6.4 mg with dacarbazine and interferon alfa (Maio et al., 2010). Sepsis trials dosed much more intensively: 1.6 mg every 12 hours for the first 5 days then daily in ETASS (Wu et al., 2013), and every 12 hours for 7 days in the phase 3 (Wu et al., 2025). The volunteer pharmacokinetic study used 900 mcg/m2, with tmax 1 to 2 hours and no accumulation over 5 days (Rost et al., 1999). ### Mechanism Thymosin alpha-1 is a 28-residue acetylated peptide from the thymosin alpha fraction, used clinically as the synthetic thymalfasin. Published work describes it as an immune response modifier acting on T-cell maturation and function and on dendritic cell maturation, rather than as a receptor agonist with a single defined target (Goldstein and Goldstein, 2009). In the sepsis trials the measured pharmacodynamic endpoint was monocyte HLA-DR expression, which rose at days 3 and 7 relative to control (Wu et al., 2013), and the phase 3 found no difference in any clinical or safety outcome (Wu et al., 2025). Its own developers describe the pleiotropic effect profile as an obstacle to defining the pharmacology (Tuthill, 2007). ### Evidence Clinical: at least one published human trial or an approved drug - Randomised trial in 98 patients with chronic hepatitis B: 1.6 mg subcutaneously twice weekly for 26 weeks gave a higher complete virological response at 18 months than no treatment, with histological improvement and no significant side effects (Chien et al., 1998) - Placebo-controlled phase 3 in 97 HBeAg-positive patients at the same dose for 6 months did not confirm efficacy: 14% versus 4% complete response, not significant (Mutchnick et al., 1999) - Randomised trial in 488 patients with metastatic melanoma tested 1.6, 3.2 and 6.4 mg with dacarbazine and interferon alfa; response rates were higher in the thymalfasin arms than the control arm (Maio et al., 2010) - ETASS, 361 patients with severe sepsis, single-blind: lower 28-day all-cause mortality and higher monocyte HLA-DR expression at days 3 and 7 (Wu et al., 2013) - TESTS, 1106 patients with sepsis, double-blind placebo-controlled phase 3 at 22 Chinese centres: 28-day mortality 23.4% versus 24.1%, hazard ratio 0.99, no secondary or safety outcome differed (Wu et al., 2025) - Human-trial status: approved in over 30 countries for hepatitis B and C and as an immune adjuvant (Tuthill, 2007; Goldstein and Goldstein, 2009), with no US application on file. Subcutaneous pharmacokinetics were characterised in 9 healthy volunteers at 900 mcg/m2 (Rost et al., 1999) ### References - [Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Chien RN, Liaw YF, Chen TC, Yeh CT, Sheen IS, Hepatology, 1998](https://doi.org/10.1002/hep.510270527) - [Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. Mutchnick MG, Lindsay KL, Schiff ER, et al., Journal of Viral Hepatitis, 1999](https://doi.org/10.1046/j.1365-2893.1999.00181.x) - [Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers. Rost KL, Wierich W, Masayuki F, Tuthill CW, Horwitz DL, Herrmann WM, International Journal of Clinical Pharmacology and Therapeutics, 1999](https://pubmed.ncbi.nlm.nih.gov/10027483/) - [Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. Maio M, Mackiewicz A, Testori A, et al., Journal of Clinical Oncology, 2010](https://doi.org/10.1200/JCO.2009.25.5208) - [The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Wu J, Zhou L, Liu J, et al., Critical Care, 2013](https://doi.org/10.1186/cc11932) - [The efficacy and safety of thymosin alpha1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. Wu J, Pei F, Zhou L, et al., BMJ, 2025](https://doi.org/10.1136/bmj-2024-082583) - [Issues in pharmaceutical development of thymosin alpha1 from preclinical studies through marketing. Tuthill C, Annals of the New York Academy of Sciences, 2007](https://doi.org/10.1196/annals.1415.007) - [From lab to bedside: emerging clinical applications of thymosin alpha 1. Goldstein AL, Goldstein AL, Expert Opinion on Biological Therapy, 2009](https://doi.org/10.1517/14712590902911412) ### Side effects Injection-site reactions are the commonly reported effect. In the 98-patient hepatitis B trial no significant side effects were observed (Chien et al., 1998), and in the 1106-patient double-blind sepsis trial no safety outcome differed from placebo (Wu et al., 2025), which is the largest controlled safety dataset available. Because it modifies T-cell function, caution is warranted in autoimmune disease and in transplant recipients on immunosuppression; this is a mechanistic concern, not a reported event rate. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Under 3 h (human, subcutaneous; tmax 1 to 2 h, no accumulation over 5 days, n=9; Rost et al., 1999) - Bioavailability: Well absorbed subcutaneously with tmax 1 to 2 h and an apparent distribution volume of 30 to 40 L, consistent with extracellular distribution; absolute bioavailability was not determined and differed between formulations (Rost et al., 1999) - Molecular weight: 3108.27 Da - Sequence: [Ac]SDAAVDTSSEITTKDLKEKKEVVEEAEN ### Stacks with - [LL-37](https://peptidelabs.app/peptides/ll-37/) - [Thymulin](https://peptidelabs.app/peptides/thymulin/) ### Categories - [Immune](https://peptidelabs.app/peptides/category/immune/) ## Thymosin Beta-4 Fragment Capsule URL: https://peptidelabs.app/peptides/thymosin-beta-4-fragment-capsule/ Also known as: TB-4 fragment 17-23, Ac-LKKTETQ, Thymosin beta-4 fragment (LKKTETQ) Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Oral capsule formulation of a Thymosin Beta-4 active fragment sold for recovery; short peptides are poorly absorbed from the gut and no human data support this route. An oral capsule of Ac-LKKTETQ, the actin-binding fragment (residues 17 to 23) of thymosin beta-4 and the peptide found in products sold as TB-500 (Esposito 2012). Every healing result behind it comes from injected or topical dosing in animals, or from the full-length protein in humans: the fragment matched the parent protein for endothelial migration and aortic sprouting at about 50 nM and for dermal repair in aged mice (Philp 2003a; Philp 2003b). No published study has measured absorption, plasma levels or efficacy of an oral capsule of this fragment in any species, and a 2024 study found it rapidly degraded in serum (Rahaman 2024). Short unprotected peptides are degraded by gastric acid and gut peptidases, so oral delivery of related peptides has needed nanoparticle or hydrogel carriers. FDA reports no human exposure data for this substance by any route. ### Benefits Marketed for recovery and tissue repair; oral efficacy unproven ### Dosing reference - Research dose: 750 mcg to 1.5 mg daily: vendor and community range, no published human dose and no oral study of this peptide in any species - Range: 750 to 1500 mcg, 1x daily Oral capsule of Ac-LKKTETQ. No published study has dosed this peptide orally in any species, so neither the dose nor the route has support; animal results used injection or topical application. ### Mechanism The product is the heptapeptide Ac-LKKTETQ, which carries the G-actin-binding motif of thymosin beta-4. In endothelial migration and chick aortic-arch sprouting assays the motif was necessary and sufficient for the angiogenic activity of the parent protein and matched it at about 50 nM (Philp 2003a), and it promoted dermal repair in aged mice (Philp 2003b). Activities mapped to other parts of thymosin beta-4 do not belong to it: the cell-survival and antifibrotic actions attributed to Ac-SDKP come from the N-terminal end of the protein (Sosne 2010; Cavasin 2006). Nothing is known about what reaches the circulation after oral dosing, so the mechanism as sold is unestablished. ### Evidence Anecdotal: no peer-reviewed data - Commercial TB-500 material was shown by mass spectrometry to contain the N-terminally acetylated 17-23 fragment of thymosin beta-4, Ac-LKKTETQ (Esposito et al., 2012) - The seven-residue actin-binding motif was necessary and sufficient for the angiogenic activity of thymosin beta-4 in endothelial migration and aortic-arch sprouting assays at about 50 nM (Philp et al., 2003) - The synthetic LKKTETQ peptide promoted dermal wound repair in aged mice comparably to full-length thymosin beta-4; dosing was topical or intraperitoneal, not oral (Philp et al., 2003) - Ac-SDKP, the separate N-terminal fragment this record previously named, has its own cardiac and antifibrotic literature and is not the peptide sold here (Cavasin, 2006) - Ac-LKKTETQ was rapidly metabolized in human serum and in rats, and only the metabolite Ac-LKKTE showed significant wound-healing activity in fibroblasts (Rahaman et al., 2024) - Human-trial status: no trial of this fragment by any route, and no study of oral dosing in any species. FDA states it has identified no human exposure data for the LKKTETQ fragment ### References - [Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012](https://doi.org/10.1002/dta.1402) - [The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003](https://doi.org/10.1096/fj.03-0121fje) - [Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Philp D, Badamchian M, Scheremeta B, et al., Wound Repair and Regeneration, 2003](https://doi.org/10.1046/j.1524-475x.2003.11105.x) - [Biological activities of thymosin beta4 defined by active sites in short peptide sequences. Sosne G, Qiu P, Goldstein AL, Wheater M, FASEB Journal, 2010](https://doi.org/10.1096/fj.09-142307) - [Therapeutic potential of thymosin-beta4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in cardiac healing after infarction. Cavasin MA, American Journal of Cardiovascular Drugs, 2006](https://doi.org/10.2165/00129784-200606050-00003) - [Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. Rahaman KA, Muresan AR, Min H, et al., Journal of Chromatography B, 2024](https://doi.org/10.1016/j.jchromb.2024.124033) ### Side effects No human safety data exists and oral bioavailability of the fragment is unproven. Injectable thymosin beta-4 is associated with injection-site irritation and transient fatigue. Because the parent molecule promotes angiogenesis, use with active or suspected malignancy is theoretically inadvisable. ### Storage - Storage: Room temperature - Lyophilized: 12+ months ### Pharmacology - Half-life: Not measured. Rapidly degraded in human serum and in rats, with Ac-LKK detectable in rat urine to 72 h (Rahaman 2024) - Molecular weight: 889.02 Da - Sequence: Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ, 7 aa; residues 17 to 23 of thymosin beta-4) ### Stacks with - [BPC-157](https://peptidelabs.app/peptides/bpc-157/) - [GHK-Cu](https://peptidelabs.app/peptides/ghk-cu/) ### Categories - [Healing & Recovery](https://peptidelabs.app/peptides/category/healing-recovery/) ## Thymulin URL: https://peptidelabs.app/peptides/thymulin/ Also known as: Facteur Thymique Sérique, FTS, Serum Thymic Factor Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Zinc-bound nonapeptide hormone secreted by thymic epithelial cells; drives T-cell differentiation and shows immunomodulatory and anti-inflammatory effects in animal studies. Thymulin is a zinc-dependent nonapeptide secreted by thymic epithelial cells, purified from pig serum in 1977 as facteur thymique serique (Dardenne et al., 1977). Zinc binding is what makes it active (Dardenne et al., 1982). Circulating levels peak in childhood and decline from adolescence onward (Consolini et al., 2000). Rodent work reports anti-inflammatory and antinociceptive effects in the central nervous system (Safieh-Garabedian et al., 2003), and a 2026 mouse study found it restrains age-associated myeloid inflammation and improves response to anti-PD-L1 therapy (Kanemaru et al., 2026). Human dosing data amount to one 1982 case series of three immunodeficient children given intravenous synthetic FTS (Bordigoni et al., 1982). No trial and no pharmacokinetic study exists. ### Benefits Zinc-dependent T-cell maturation factor (in vitro); anti-inflammatory and antinociceptive effects and improved tumour immunotherapy response (rodent); one 3-patient human case series ### Dosing reference - Research dose: 1 to 10 mcg daily (vendor/community range, no published human dose) - Range: 1 to 10 mcg, 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 1 mg Activity depends on bound zinc at a 1:1 molar ratio; the metal-free peptide is inactive in the rosette assay (Dardenne et al., 1982). No human dosing protocol exists. The single human report gave synthetic FTS intravenously to three immunodeficient children, with immunological gains that regressed when dosing was interrupted (Bordigoni et al., 1982). Rodent central dosing used 0.1 to 1 mcg intracerebroventricularly (Safieh-Garabedian et al., 2003). The low-microgram range in circulation is community convention, not a tested dose. ### Mechanism Thymulin is a nonapeptide first purified from pig serum as facteur thymique serique and sequenced in 1977 (Dardenne et al., 1977; Pleau et al., 1977). Its activity depends on bound zinc: removing metal ions with a chelating resin abolished activity in the rosette assay, and zinc restored it best at a 1:1 metal-to-peptide ratio, which is why the active zinc-bound form carries the name thymulin (Dardenne et al., 1982). Plasma levels track thymic function across life, peaking in childhood and falling from adolescence (Consolini et al., 2000). In rodents, thymulin and its peptide analog are anti-inflammatory and antinociceptive in the central nervous system (Safieh-Garabedian et al., 2003). Recent mouse work identifies suppression of NF-kappaB-driven cytokine production by pro-inflammatory myeloid cells as a mechanism (Kanemaru et al., 2026). ### Evidence Preclinical: animal or in vitro data only - The circulating thymic factor was purified from pig serum and sequenced as pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn; synthetic peptide reproduced the biological activity (Dardenne et al., 1977; Pleau et al., 1977) - Chelating metal ions abolished activity and zinc restored it at a 1:1 molar ratio, which is why the active form was renamed thymulin (FTS-Zn) (Dardenne et al., 1982) - Three immunodeficient children given synthetic FTS intravenously showed improved cell-mediated immunity tests and the appearance of serum IgA, which regressed when dosing stopped and returned when it restarted (Bordigoni et al., 1982) - Plasma thymulin is detectable at birth, peaks at 5 to 10 years, falls from adolescence and reaches its lowest level by about 36 years in 93 healthy individuals (Consolini et al., 2000) - Intracerebroventricular pretreatment in rats reduced endotoxin-induced hyperalgesia dose-dependently and altered brain cytokine levels (Safieh-Garabedian et al., 2003) - Human-trial status: no randomised trial of thymulin exists. The only human dosing report is a 3-patient case series from 1982. Recent work is preclinical: thymulin suppressed age-associated myeloid inflammation and improved tumour control in mice (Kanemaru et al., 2026) ### References - [Structural study of circulating thymic factor: a peptide isolated from pig serum. II. Amino acid sequence. Pleau JM, Dardenne M, Blouquit Y, Bach JF, Journal of Biological Chemistry, 1977](https://pubmed.ncbi.nlm.nih.gov/914862/) - [Contribution of zinc and other metals to the biological activity of the serum thymic factor. Dardenne M, Pleau JM, Nabarra B, et al., Proceedings of the National Academy of Sciences, 1982](https://doi.org/10.1073/pnas.79.17.5370) - [Improvement of cellular immunity and IgA production in immunodeficient children after treatment with synthetic serum thymic factor (FTS). Bordigoni P, Faure G, Bene MC, Dardenne M, Bach JF, Duheille J, Olive D, The Lancet, 1982](https://doi.org/10.1016/s0140-6736(82)90271-9) - [Distribution of age-related thymulin titres in normal subjects through the course of life. Consolini R, Legitimo A, Calleri A, Milani M, Clinical and Experimental Immunology, 2000](https://doi.org/10.1046/j.1365-2249.2000.01315.x) - [Thymulin reverses inflammatory hyperalgesia and modulates the increased concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection. Safieh-Garabedian B, Ochoa-Chaar CI, Poole S, et al., Neuroscience, 2003](https://doi.org/10.1016/s0306-4522(03)00500-1) - [Physiology and therapeutic potential of the thymic peptide thymulin. Reggiani PC, Schwerdt JI, Console GM, et al., Current Pharmaceutical Design, 2014](https://doi.org/10.2174/1381612820666140130211157) - [Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy. Kanemaru H, Luong S, Yamamoto Y, Mizukami Y, Ito F, Nature Communications, 2026](https://doi.org/10.1038/s41467-026-75383-0) ### Side effects There is no safety dataset. The only human report is three immunodeficient children given intravenous synthetic FTS in 1982, which describes immunological changes and no adverse events (Bordigoni et al., 1982). No trial, no repeat-dose study and no pharmacokinetics exist in any species at a dose relevant to use. Because it modifies T-cell function, caution is warranted in autoimmune disease and with immunosuppressive therapy; that is mechanistic, not observed. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: Not measured. No pharmacokinetic study of thymulin exists in any species. - Bioavailability: Not measured by any route. Human and rodent dosing used intravenous or intracerebroventricular administration; activity requires bound zinc (Dardenne et al., 1982; Bordigoni et al., 1982). - Molecular weight: 858.9 Da - Sequence: [pGlu]AKSQGGSN (zinc-bound form is the active one) ### Stacks with - [Thymosin Alpha-1](https://peptidelabs.app/peptides/thymosin-alpha-1/) - [LL-37](https://peptidelabs.app/peptides/ll-37/) ### Categories - [Immune](https://peptidelabs.app/peptides/category/immune/) ## Thyrotropin TRH URL: https://peptidelabs.app/peptides/thyrotropin-trh/ Also known as: Protirelin, Thyroliberin, Thyrotropin releasing factor, TRF, Thyrel TRH, Thypinone Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide that triggers pituitary TSH and prolactin release; used clinically as a diagnostic challenge of the thyroid axis. Thyrotropin-Releasing Hormone (TRH, protirelin) is a hypothalamic tripeptide (pGlu-His-Pro-NH2) that stimulates the pituitary to release TSH and prolactin, indirectly driving thyroid hormone output. Its established human use is diagnostic - a 200-500 mcg IV bolus to test pituitary-thyroid reserve. TRH receptors are also present in the CNS and research has explored transient effects on mood, arousal and motor function in depression and spinal injury, though no therapeutic indication has been established. Note the entry name conflates two different molecules: thyrotropin is TSH, a pituitary glycoprotein hormone, while TRH is the hypothalamic releasing tripeptide described here. Same molecule as the catalog entry Protirelin. ### Benefits Diagnostic stimulation of the pituitary-thyroid axis; research interest in mood and arousal ### Dosing reference - Research dose: 200-500 mcg (diagnostic IV bolus) - Range: 200 to 500 mcg, Diagnostic or 1x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 20 mg, 50 mg Human dosing is a single intravenous bolus for the TSH-stimulation test; published dose-response work used 25 to 800 mcg IV, with 200 to 500 mcg the usual diagnostic dose (Garbutt 1994; Doi 2007). Intrathecal 500 mcg has been used in depression research (Marangell 1997). Effects within minutes of injection include a transient blood pressure change, flushing, nausea, an urge to urinate and an odd taste, and prolactin rises acutely. No repeated-dosing protocol has been established in humans. ### Mechanism TRH is a hypothalamic tripeptide (pGlu-His-Pro-NH2) that reaches the anterior pituitary through the portal circulation and stimulates TSH release from thyrotrophs through the Gq-coupled TRH receptor and phospholipase C signalling; it also releases prolactin (Joseph-Bravo 2015; Gary 2003). TSH in turn drives thyroid hormone output, and thyroid hormone feeds back on hypophysiotropic TRH neurons (Joseph-Bravo 2015). Circulating TRH is degraded quickly, with a plasma half-life near 7 minutes in humans (Iversen 1988). TRH receptors are also expressed in the CNS, and intrathecal dosing produced short-lived mood effects in refractory depression, which is the basis for calling TRH a proposed homeostatic modulator (Marangell 1997; Gary 2003). ### Evidence Clinical: at least one published human trial or an approved drug - Protirelin injection was approved by the FDA as a diagnostic agent for assessing pituitary TSH reserve: Thypinone (NDA 017638, Abbott, approved 5 November 1976) and Thyrel TRH (NDA 018087, Ferring, approved 18 July 1978); both are listed as discontinued - Human intravenous pharmacokinetics: plasma half-life 6.6 ± 1.5 min and clearance 1532 ± 423 mL/min in 14 healthy subjects (Iversen, 1988) - Dose-response study in 13 patients with major depression and 12 matched controls using 25, 100, 500 and 800 mcg IV: depressed men had blunted TSH and prolactin responses across all doses (Garbutt et al., 1994) - 500 mcg intrathecally in 8 medication-free patients with refractory depression, double-blind against sham lumbar puncture: 5 of 8 responded and suicidality fell, but the effect was short-lived (Marangell et al., 1997) - Pituitary apoplexy, meaning haemorrhage into an existing pituitary adenoma, is reported after TRH stimulation testing (Wang et al., 2007) - Human-trial status: human use is diagnostic only and no therapeutic indication is approved; the TRH analog taltirelin is approved in Japan and 5 mg twice daily for 24 weeks gave a small ataxia-score benefit in spinocerebellar degeneration (n=149, Cho et al., 2025) ### References - [The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: implications for TRH-based therapeutics. Gary KA, Sevarino KA, Yarbrough GG, Prange AJ Jr, Winokur A, Journal of Pharmacology and Experimental Therapeutics, 2003](https://doi.org/10.1124/jpet.102.044040) - [Intra- and extravascular turnover of thyrotrophin-releasing hormone in normal man. Iversen E, Journal of Endocrinology, 1988](https://doi.org/10.1677/joe.0.1180511) - [60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary-thyroid axis. Joseph-Bravo P, Jaimes-Hoy L, Uribe RM, Charli JL, Journal of Endocrinology, 2015](https://doi.org/10.1530/JOE-15-0124) - [Dose-response studies with protirelin. Garbutt JC, Mayo JP, Little KY, et al., Archives of General Psychiatry, 1994](https://doi.org/10.1001/archpsyc.1994.03950110035006) - [Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients. Marangell LB, George MS, Callahan AM, et al., Archives of General Psychiatry, 1997](https://doi.org/10.1001/archpsyc.1997.01830150034007) - [Pituitary apoplexy after thyrotropin-releasing hormone stimulation test in a patient with pituitary macroadenoma. Wang HF, Huang CC, Chen YF, Ho DM, Lin HD, Journal of the Chinese Medical Association, 2007](https://doi.org/10.1016/S1726-4901(08)70026-1) - [TRH stimulation when basal TSH is within the normal range: is there "sub-biochemical" hypothyroidism?. Doi SA, Issac D, Abalkhail S, Al-Qudhaiby MM, Hafez MF, Al-Shoumer KA, Clinical Medicine & Research, 2007](https://doi.org/10.3121/cmr.2007.756) - [Efficacy and Safety of Taltirelin Hydrate in Patients With Ataxia Due to Spinocerebellar Degeneration. Cho JW, Lee JY, Kim HJ, et al., Journal of Movement Disorders, 2025](https://doi.org/10.14802/jmd.24127) ### Side effects This is a diagnostic agent with acute hemodynamic effects: transient blood pressure change, flushing, nausea, a strong urge to urinate, and an odd taste occur within minutes of injection. Pituitary apoplexy, meaning hemorrhage into an existing pituitary tumor, is a rare but life-threatening reported complication. It also acutely raises prolactin. ### Storage - Storage: Refrigerate 2-8°C (36-46°F); general lyophilised-peptide guidance, no compound-specific CoA located - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: 6.6 ± 1.5 min plasma (human, IV constant infusion, n=14); degradation half-life in serum in vitro 16.8 ± 9.4 min (Iversen 1988) - Bioavailability: IV: plasma clearance 1532 ± 423 mL/min in healthy adults (Iversen 1988). Intrathecal dosing has been used in humans to bypass poor blood-brain-barrier penetration (Marangell 1997). No oral, intranasal or subcutaneous bioavailability figure located. - Molecular weight: 362.38 Da - Sequence: pGlu-His-Pro-NH2 (pyroglutamate-histidine-proline amide) ### Categories - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) ## Tirzepatide URL: https://peptidelabs.app/peptides/tirzepatide/ Also known as: Mounjaro, Zepbound, LY3298176 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Dual GIP and GLP-1 receptor agonist; FDA-approved for type 2 diabetes (2022) and obesity (2023). In SURMOUNT-1, 15 mg weekly gave 20.9% weight loss at 72 weeks versus 3.1% with placebo. Tirzepatide (LY3298176) is a 39-residue peptide based on the GIP sequence with Aib at positions 2 and 13, a C-terminal amide and a C20 fatty diacid on Lys20, giving a half-life of about 5 days (Coskun 2018). In SURMOUNT-1, 5, 10 and 15 mg weekly gave 15.0%, 19.5% and 20.9% weight loss over 72 weeks versus 3.1% (Jastreboff 2022). It lowered HbA1c more than semaglutide 1 mg in SURPASS-2 (Frías 2021) and gave 20.2% versus 13.7% weight loss against semaglutide 2.4 mg in SURMOUNT-5 (Aronne 2025). FDA approved Mounjaro for type 2 diabetes in 2022 and Zepbound for weight in 2023, with obstructive sleep apnea added later; both are marketed. ### Benefits Weight loss (human RCTs; 20.9% at 15 mg), lower HbA1c in type 2 diabetes (human RCTs), greater weight and HbA1c reduction than semaglutide (head-to-head RCTs), obstructive sleep apnea (FDA indication) ### Dosing reference - Research dose: 2.5-15mg weekly - Range: 2500 to 15000 mcg, 1x weekly - Reconstitution: 1.5 mL bacteriostatic water - Common vial sizes: 5 mg, 10 mg, 15 mg Subcutaneous, once weekly. Label titration starts at 2.5 mg weekly for 4 weeks and rises in 2.5 mg steps at least 4 weeks apart to a maintenance dose of 5, 10 or 15 mg (Zepbound label). Coadministration with other GLP-1 receptor agonists is not recommended by the label. ### Mechanism Tirzepatide activates both the GIP and GLP-1 receptors. Together these raise glucose-dependent insulin secretion, lower glucagon, slow gastric emptying and reduce food intake (Zepbound label). In obese mice it lowered weight more than a selective GLP-1 agonist, which the discovery team attributes to combined receptor activation (Coskun 2018). A C20 fatty diacid on Lys20 binds albumin (99% bound), supporting weekly dosing (Coskun 2018; label). The term 'twincretin' and claims of synergy beyond GLP-1 agonists in humans rest on the head-to-head trials, not on a defined mechanism. ### Evidence Clinical: at least one published human trial or an approved drug - SURMOUNT-1 (n=2539, 72 weeks): 15.0%, 19.5% and 20.9% weight loss at 5, 10 and 15 mg versus 3.1% with placebo (Jastreboff et al., 2022) - SURPASS-1 (n=478, 40 weeks, type 2 diabetes): HbA1c fell 1.87 to 2.07 percentage points versus +0.04 with placebo (Rosenstock et al., 2021) - SURPASS-2 (type 2 diabetes): greater HbA1c reduction than semaglutide 1 mg at all doses (Frías et al., 2021) - SURMOUNT-5 (n=751, 72 weeks): 20.2% weight loss versus 13.7% with semaglutide 2.4 mg (Aronne et al., 2025) - Status: FDA-approved and marketed. Mounjaro (type 2 diabetes, 2022), Zepbound (weight, 2023; obstructive sleep apnea added) ### References - [Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff AM, Aronne LJ, Ahmad NN, et al., New England Journal of Medicine, 2022](https://doi.org/10.1056/NEJMoa2206038) - [Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Rosenstock J, Wysham C, Frías JP, et al., Lancet, 2021](https://doi.org/10.1016/S0140-6736(21)01324-6) - [LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Coskun T, Sloop KW, Loghin C, et al., Molecular Metabolism, 2018](https://doi.org/10.1016/j.molmet.2018.09.009) - [Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Frías JP, Davies MJ, Rosenstock J, et al., New England Journal of Medicine, 2021](https://doi.org/10.1056/NEJMoa2107519) - [Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. Aronne LJ, Horn DB, le Roux CW, et al., New England Journal of Medicine, 2025](https://doi.org/10.1056/NEJMoa2416394) ### Side effects Nausea, vomiting, diarrhea, and constipation dominate, particularly during titration. Reported serious risks include pancreatitis, gallbladder disease, severe gastroparesis, and aspiration risk during anesthesia from delayed gastric emptying. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2; rodent studies showed thyroid C-cell tumors. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months refrigerated - Reconstituted: 30 days refrigerated ### Pharmacology - Half-life: ~5 days (116.7 h in phase 1; 5 to 6 days in adults with overweight or obesity, subcutaneous; Zepbound label) - Bioavailability: Subcutaneous: ~80% - Molecular weight: 4813.45 Da - Sequence: Y[Aib]EGTFTSDYSI[Aib]LDKIAQK[linker-C20 diacid]AFVQWLIAGGPSSGAPPPS[NH2] ### Categories - [Fat Loss](https://peptidelabs.app/peptides/category/fat-loss/) - [Metabolic](https://peptidelabs.app/peptides/category/metabolic/) - [Appetite](https://peptidelabs.app/peptides/category/appetite/) ## Tripeptide-29 (Collagen Hexapeptide) URL: https://peptidelabs.app/peptides/tripeptide-29-collagen-hexapeptide/ Also known as: Glycyl-prolyl-hydroxyproline, Gly-Pro-Hyp, GPH peptide, Collagen Tripeptide Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Collagen-derived tripeptide Gly-Pro-Hyp; it preserved collagen I gene expression in stressed fibroblasts in vitro and oral dosing reduced UV skin damage in mice. No topical study exists. Tripeptide-29 is the INCI name for glycyl-prolyl-hydroxyproline, the repeating unit of the collagen triple helix (PubChem lists Tripeptide-29 as a synonym). The product name's 'Collagen Hexapeptide' is wrong: this is a three-residue peptide. Nearly all research on it comes from oral collagen supplements: it appears in human blood after collagen hydrolysate is eaten (Yazaki et al., 2017), its oral bioavailability in rats is 4.4% (Won et al., 2024), and oral Gly-Pro-Hyp reduced UV skin damage in mice (Yang et al., 2024). In vitro it kept collagen I, elastin and fibronectin gene expression up in fibroblasts exposed to hydrogen peroxide (Chae et al., 2023). No study of Gly-Pro-Hyp applied to skin was found. ### Benefits Preserved collagen I, elastin and fibronectin gene expression under oxidative stress (fibroblasts, in vitro), reduced UV-induced skin damage after oral dosing (mouse); no topical data ### Dosing reference - Research dose: Topical; no published topical concentration or human dose. Topical only as sold. No topical concentration has been published. Animal studies dosed it orally or IV (rat: 5 mg/kg IV, 100 mg/kg intragastric for PK). ### Mechanism Proposed. Gly-Pro-Hyp prevented the hydrogen-peroxide-induced drop in COL1A, elastin and fibronectin gene expression in dermal fibroblasts (Chae et al., 2023). In UV-exposed mice given it orally, network analysis suggested JUN, FOS, IL-17 and TNF signaling, which was not tested directly (Yang et al., 2024). Repeats of the (Gly-Pro-Hyp)n motif in collagen bind keratinocyte growth factor (Ruehl et al., 2002). In mouse skin, oral Gly-Pro-Hyp is largely converted to the dipeptide Pro-Hyp (Yazaki et al., 2017). The old decorin, proteoglycan and crosslinking claims have no source. ### Evidence Preclinical: animal or in vitro data only - Prevented hydrogen-peroxide-induced loss of COL1A, elastin and fibronectin gene expression in human dermal fibroblasts (Chae et al., 2023) - Oral Gly-Pro-Hyp reduced UV-induced photoaging in mice, comparable to a tripeptide-rich collagen hydrolysate on an equal-hydroxyproline basis (Yang et al., 2024) - Rat PK after IV (5 mg/kg) and intragastric (100 mg/kg) dosing: oral bioavailability 4.4%, partly converted to Pro-Hyp (Won et al., 2024) - Detected in human plasma after a tripeptide-rich collagen hydrolysate; in mice, pure Gly-Pro-Hyp raised Pro-Hyp in skin (Yazaki et al., 2017) - Human-trial status: no trial of Tripeptide-29 applied to skin; human data are oral collagen hydrolysates containing it among many peptides ### References - [Oral Ingestion of AP Collagen Peptide Leads to Systemic Absorption of Gly-Pro-Hyp, Alleviating H(2)O(2)-Induced Dermal Fibroblast Aging. Chae M, Moon CY, Lim SH, Yamashita Y, et al., Journal of medicinal food, 2023](https://doi.org/10.1089/jmf.2022.K.0149) - [Effects of collagen hydrolysates on UV-induced photoaging mice: Gly-Pro-Hyp as a potent anti-photoaging peptide. Yang D, Liu Q, Xu Q, Zheng L, et al., Food & function, 2024](https://doi.org/10.1039/d3fo04949c) - [Pharmacokinetics of collagen dipeptides (Gly-Pro and Pro-Hyp) and tripeptides (Gly-Pro-Hyp) in rats. Won J, Kang J, Noh K, Chung HC, et al., Journal of food science, 2024](https://doi.org/10.1111/1750-3841.16871) - [Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin. Yazaki M, Ito Y, Yamada M, Goulas S, et al., Journal of agricultural and food chemistry, 2017](https://doi.org/10.1021/acs.jafc.6b05679) - [The epithelial mitogen keratinocyte growth factor binds to collagens via the consensus sequence glycine-proline-hydroxyproline. Ruehl M, Somasundaram R, Schoenfelder I, Farndale RW, et al., The Journal of biological chemistry, 2002](https://doi.org/10.1074/jbc.M202335200) ### Side effects No topical safety study has been published. Gly-Pro-Hyp is a normal product of collagen digestion and appears in human blood after collagen hydrolysate is eaten (Yazaki et al., 2017). Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No topical data. Rat IV and intragastric PK published, with flip-flop kinetics after oral dosing (Won et al., 2024) - Bioavailability: Topical: not measured. Oral: 4.4% absolute bioavailability in rats (Won et al., 2024) - Molecular weight: 285.3 Da - Sequence: Gly-Pro-Hyp ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Triptorelin URL: https://peptidelabs.app/peptides/triptorelin/ Also known as: Decapeptyl, Trelstar, Triptodur, Triptorelin pamoate, Triptorelin acetate Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic decapeptide GnRH agonist; one dose triggers an LH and FSH surge, continued exposure suppresses them. FDA-labeled depots treat prostate cancer (Trelstar) and precocious puberty (Triptodur). Triptorelin is GnRH with D-tryptophan at position 6, which makes it far more potent and longer lived than the native hormone. A first dose causes an LH and FSH surge and a testosterone or estrogen flare; continued exposure desensitizes pituitary receptors and suppresses sex hormones to castrate levels. In the US it is approved by the FDA as Trelstar depots (3.75, 11.25 and 22.5 mg, from 2000) for advanced prostate cancer and as Triptodur (22.5 mg every 24 weeks, 2017) for central precocious puberty. Endometriosis and uterine fibroids are not US indications. A single 0.2 mg dose has been used in IVF to trigger oocyte maturation (Fauser 2002). Vendor research vials are not the labeled depots. ### Benefits Testosterone suppression in advanced prostate cancer (FDA-labeled depot), pubertal suppression in central precocious puberty (FDA-labeled depot), oocyte-maturation trigger in IVF (human trials, not a US indication), single-dose LH surge for post-cycle use (community, no trial) ### Dosing reference - Research dose: Community protocol: 100 mcg once (anecdotal). US labels cover depot products for prostate cancer and central precocious puberty only. - Range: 100 mcg, Single dose - Reconstitution: 1 mL bacteriostatic water - Common vial sizes: 0.1 mg, 2 mg A single 100 mcg dose is a community protocol (anecdotal); clinical ovulation-trigger doses are around 200 mcg. Repeated or depot exposure suppresses the HPG axis and causes hypogonadism, with hot flushes, loss of libido, mood changes and bone mineral density loss on prolonged use. The initial hormone flare can transiently worsen hormone-sensitive conditions. ### Mechanism Triptorelin is a synthetic decapeptide agonist of the GnRH receptor. In vitro it was 100-fold more active than native GnRH at releasing LH from rat pituitary cells and 20-fold more active at displacing labeled GnRH from pituitary receptors (Trelstar label). Acute exposure releases LH and FSH; repeated or depot exposure desensitizes the gonadotrophs, and the label reports LH at or below 1 IU/L two hours after repeat dosing in 98% of men, which is the basis of medical castration. The post-cycle use relies on the acute surge from a single dose without the follow-on suppression; that rationale is mechanistic and untested. ### Evidence Clinical: at least one published human trial or an approved drug - Triptorelin pamoate monthly versus leuprolide in men with advanced prostate cancer: comparable castration rates (Heyns et al., 2003); the label reports castration by day 29 in 91.2% on 3.75 mg - Single-arm phase 3 study of the 6-month 22.5 mg depot in locally advanced and metastatic prostate cancer (Lundström et al., 2009) - Triptorelin 22.5 mg every 24 weeks in 44 children with central precocious puberty kept stimulated LH prepubertal in 93% or more at every visit (Klein et al., 2016) - IV pharmacokinetics in healthy men and in renal or hepatic insufficiency (Müller et al., 1997) - GnRH agonist trigger (triptorelin 0.2 mg) after ganirelix co-treatment in IVF (Fauser et al., 2002) - Human-trial status: approved by the FDA as Trelstar (2000, prostate cancer) and Triptodur (2017, central precocious puberty), both marketed; no trial has tested a single dose for post-cycle recovery ### References - [Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. Heyns CF, Simonin MP, Grosgurin P, et al., BJU International, 2003](https://doi.org/10.1046/j.1464-410x.2003.04308.x) - [Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study. Lundström EA, Rencken RK, van Wyk JH, et al., Clinical Drug Investigation, 2009](https://doi.org/10.2165/11319690-000000000-00000) - [Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. Klein K, Yang J, Aisenberg J, et al., Journal of Pediatric Endocrinology & Metabolism, 2016](https://doi.org/10.1515/jpem-2015-0376) - [Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency. Müller FO, Terblanchè J, Schall R, et al., British Journal of Clinical Pharmacology, 1997](https://doi.org/10.1046/j.1365-2125.1997.t01-1-00592.x) - [Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. Fauser BC, de Jong D, Olivennes F, et al., Journal of Clinical Endocrinology & Metabolism, 2002](https://doi.org/10.1210/jcem.87.2.8197) ### Side effects Trelstar label (men): hot flushes, skeletal pain, impotence or erectile dysfunction, headache, leg edema and testicular atrophy; an initial testosterone flare that can transiently worsen prostate cancer; hypersensitivity reactions, metabolic changes, cardiovascular disease, convulsions, severe skin reactions and QT prolongation. Triptodur label (children): injection-site reactions, vaginal bleeding after the first dose, hot flush, headache, psychiatric events, convulsions and pseudotumor cerebri. Long-term suppression lowers bone density. ### Storage - Storage: Refrigerated (2-8°C) - Lyophilized: 24+ months at room temperature - Reconstituted: 28 days refrigerated ### Pharmacology - Half-life: IV in healthy men: three phases of about 6 min, 45 min and 3 h (Trelstar label; Müller 1997). IM depot: peak at 1 to 3 h, release over 4, 12 or 24 weeks - Bioavailability: IM depot in men with prostate cancer: mean peak 28 to 44 ng/mL at 1 to 3 h, no accumulation over 9 to 12 months (Trelstar label). After 0.5 mg IV, 41.7% is excreted intact in urine. No SC bioavailability figure is published. - Molecular weight: 1311.45 Da - Sequence: pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 ### Stacks with - [Gonadorelin (GnRH)](https://peptidelabs.app/peptides/gonadorelin-gnrh/) - [Kisspeptin-10](https://peptidelabs.app/peptides/kisspeptin-10/) ### Categories - [Hormonal](https://peptidelabs.app/peptides/category/hormonal/) - [Fertility](https://peptidelabs.app/peptides/category/fertility/) ## Vesilute URL: https://peptidelabs.app/peptides/vesilute/ Also known as: Vesilut, ED, Glu-Asp Evidence level: Anecdotal Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic dipeptide ED (Glu-Asp), listed by its developers as Vesilut; it appears only in transporter docking studies, and no published study supports its bladder label. The name implies a bladder peptide, but no published study tested ED on bladder tissue, urothelium or urinary function, and the developing group's own table gives no citation for the bladder label (Khavinson 2022). The old record stored KED, which is Vesugen; the developers list Vesilut as the dipeptide ED (Glu-Asp). The only indexed papers naming it are docking studies of peptide transport (Khavinson 2022, 2023). No animal, cell or human study has been published. ### Benefits No published biological effect in any model; transport by PEPT and LAT family carriers predicted by docking (in silico) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. No published dose in any species. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. ### Mechanism Unknown; no mechanism has been studied. Docking predicts the dipeptide can be carried by PEPT and LAT family transporters (Khavinson 2022, 2023). The old bladder, detrusor and urothelial claims had no source. ### Evidence Anecdotal: no peer-reviewed data - Listed as Vesilut (ED) in the developing group's table of peptide bioregulators, with no citation for its bladder label (Khavinson et al., 2022) - Docking predicted transport by PEPT and LAT family carriers (Khavinson et al., 2022) - Included among 26 ultrashort peptides docked to LAT and PEPT family transporters (Khavinson et al., 2023) - Human-trial status: none, and no animal or cell study has been published ### References - [Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers. Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, et al., International Journal of Molecular Sciences, 2022](https://doi.org/10.3390/ijms23147733) - [Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters. Khavinson VK, Linkova NS, Rudskoy AI, Petukhov MG, Biomolecules, 2023](https://doi.org/10.3390/biom13030552) ### Side effects No safety data in any species; the compound has not been tested in cells, animals or people. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species; docking only (Khavinson 2022, 2023) - Molecular weight: 262.22 Da - Sequence: ED (Glu-Asp) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Vesugen URL: https://peptidelabs.app/peptides/vesugen/ Also known as: KED, KED peptide, Lys-Glu-Asp Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic tripeptide KED (Lys-Glu-Asp), sold as a vascular bioregulator; studied in endothelial cell cultures and a mouse Alzheimer model, with uncontrolled Russian human reports. Vesugen is the tripeptide KED (Lys-Glu-Asp) from the St. Petersburg Institute of Bioregulation and Gerontology. Cell work covers vascular endothelial cell proliferation during aging (Khavinson 2014) and molecular markers relevant to atherosclerosis and restenosis (Kozlov 2016). In a mouse model of Alzheimer's disease it was among tripeptides with reported neuroprotective effects (Khavinson 2021). Human data are uncontrolled Russian reports: 41 older patients with chronic lower-limb arterial insufficiency (Kitachev 2014), a polymorbid cohort with organic brain syndrome (Meshchaninov 2015) and truck drivers with neurotic disorders, given with Pinealon (Bashkireva 2012). No randomized trial has been published. ### Benefits Vascular endothelial cell proliferation in aging cultures (in vitro), markers in atherosclerosis and restenosis models (preclinical), neuroprotection in a mouse Alzheimer model (rodent), chronic lower-limb arterial insufficiency in older adults (human, uncontrolled, n=41) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range; not compared with the doses in the uncontrolled human reports - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. Doses in the uncontrolled Russian human reports have not been compared with this range. ### Mechanism Proposed, from the developing group. The peptide is reported to act epigenetically on vascular endothelial cell proliferation in aging cultures (Khavinson 2014) and to change molecular markers in models of atherosclerosis and restenosis (Kozlov 2016). Other work describes effects on neurogenesis genes relevant to Alzheimer's disease (Khavinson 2021) and on cells of the neuroimmunoendocrine system (Chalisova 2012). Gene regulation by direct DNA binding is the group's hypothesis and has not been tested independently. The old claims about nitric oxide and vessel tone had no source. ### Evidence Preclinical: animal or in vitro data only - In 41 older patients with chronic lower-limb arterial insufficiency, an uncontrolled study reported benefit from vascular peptide bioregulators (Kitachev et al., 2014) - Given with Pinealon to patients with chronic polymorbidity and organic brain syndrome, the peptides showed prooxidant activity and lowered CD34+ cell counts (Meshchaninov et al., 2015) - Given with Pinealon to professional truck drivers with neurotic disorders (Bashkireva et al., 2012) - Reported neuroprotective effects in a mouse model of Alzheimer's disease (Khavinson et al., 2021) - Studied for epigenetic effects on vascular endothelial cell proliferation in aging cultures (Khavinson et al., 2014) - Human-trial status: no randomized trial; the human reports are uncontrolled Russian-language studies, and nearly all work comes from the developing group ### References - [The efficacy of peptide bioregulators of vessels in lower limbs chronic arterial insufficiency treatment in old and elderly people (in Russian). Kitachev KV, Sazonov AB, Kozlov KL, Petrov KIu, et al., Advances in Gerontology (Uspekhi Gerontologii), 2014](https://pubmed.ncbi.nlm.nih.gov/25051774/) - [EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION (in Russian). Meshchaninov VN, Tkachenko EL, Zharkov SV, Gavrilov IV, et al., Advances in Gerontology (Uspekhi Gerontologii), 2015](https://pubmed.ncbi.nlm.nih.gov/26390612/) - [The peptide correction of neurotic disorders among professional truck-drivers (in Russian). Bashkireva AS, Artamonova VG, Advances in Gerontology (Uspekhi Gerontologii), 2012](https://pubmed.ncbi.nlm.nih.gov/23734521/) - [Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease. Khavinson V, Ilina A, Kraskovskaya N, Linkova N, et al., Pharmaceuticals, 2021](https://doi.org/10.3390/ph14060515) - [Peptide KED: Molecular-Genetic Aspects of Neurogenesis Regulation in Alzheimer's Disease. Khavinson VK, Lin'kova NS, Umnov RS, Bulletin of Experimental Biology and Medicine, 2021](https://doi.org/10.1007/s10517-021-05192-6) - [Molecular aspects of vasoprotective peptide KED activity during atherosclerosis and restenosis (in Russian). Kozlov KL, Bolotov II, Linkova NS, Drobintseva AO, et al., Advances in Gerontology (Uspekhi Gerontologii), 2016](https://pubmed.ncbi.nlm.nih.gov/28539025/) - [Epigenetic aspects of peptidergic regulation of vascular endothelial cell proliferation during aging (in Russian). Khavinson VKh, Tarnovskaia SI, Lin'kova NS, Guton EO, et al., Advances in Gerontology (Uspekhi Gerontologii), 2014](https://pubmed.ncbi.nlm.nih.gov/25051766/) - [Effect of tripeptide Lys-Glu-Asp on physiological activity of neuroimmunoendocrine system cells. Chalisova NI, Lopatina NG, Kamishev NG, Linkova NS, et al., Bulletin of Experimental Biology and Medicine, 2012](https://doi.org/10.1007/s10517-012-1768-7) ### Side effects No controlled safety study has been published. Given with Pinealon in an uncontrolled study, the peptides showed prooxidant activity and a fall in CD34+ cells (Meshchaninov 2015). Commonly reported (anecdotal): injection-site irritation with injectable forms. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species - Molecular weight: 390.39 Da - Sequence: Lys-Glu-Asp ### Stacks with - [Pinealon](https://peptidelabs.app/peptides/pinealon/) ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) ## Vialox (Pentapeptide-3V) URL: https://peptidelabs.app/peptides/vialox-pentapeptide-3v/ Also known as: Pentapeptide-3, Pentapeptide-3V, Vialox peptide Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Synthetic pentapeptide amide (Gly-Pro-Arg-Pro-Ala-NH2, pentapeptide-3) marketed as a nicotinic receptor antagonist for expression lines; published data are in silico and cell culture only. Vialox is Pentapharm's (now DSM's) trade name for pentapeptide-3, Gly-Pro-Arg-Pro-Ala-NH2; 'Pentapeptide-3V' is a vendor label, not an INCI name. Reviews describe it as derived from snake venom and as an acetylcholine receptor antagonist, but the only efficacy data are the manufacturer's, and no peer-reviewed study describes its anti-wrinkle effect (Errante et al., 2020). The published research is recent and from one Istanbul group: spectroscopy and docking (Akhan et al., 2025), docking plus a keratinocyte cytotoxicity assay (Akhan et al., 2026), and a cancer cell line screen (Akhan et al., 2026). No human study has been published. ### Benefits Predicted binding to SIRT1, TGF-beta receptor I and MAPK14 (in silico), no keratinocyte cytotoxicity up to 1 mg/mL (in vitro); expression-line reduction is manufacturer data, not peer reviewed ### Dosing reference - Research dose: Topical; no published concentration. Topical only. No peer-reviewed study states a use concentration; the only figures are in supplier literature. ### Mechanism Proposed by the manufacturer: competitive antagonism at the muscle nicotinic acetylcholine receptor, described as curare-like (Errante et al., 2020). No peer-reviewed receptor-binding, electrophysiology or muscle study exists. Docking and molecular dynamics predict binding to SIRT1, MMPs, TGF-beta receptor I and MAPK14 (Akhan et al., 2025; Akhan et al., 2026); none of these has been confirmed in cells or tissue. ### Evidence Preclinical: animal or in vitro data only - Docking and molecular dynamics favour SIRT1 binding; no cytotoxicity in HaCaT keratinocytes up to 1 mg/mL (Akhan et al., 2026) - DFT, FTIR and Raman characterisation with docking to TGF-beta receptor I (-8.12 kcal/mol) and MAPK14 (-8.25 kcal/mol) (Akhan et al., 2025) - Cytotoxic to MDA-MB-231 breast and PC3 prostate cancer cells in MTT assays; docking to EGFR and PI3K (Akhan et al., 2026) - Review: no published investigation of anti-wrinkle effect; efficacy data are the manufacturer's (Errante et al., 2020) - Human-trial status: no published human study; all peer-reviewed data are in silico or in vitro from one group ### References - [Integrative In Silico and In Vitro Evaluation of Vialox and Leuphasyl Pentapeptides for Antiaging Applications. Akhan D, Bicak B, Kurtur OB, Budama-Kilinc Y, et al., Chemistry & biodiversity, 2026](https://doi.org/10.1002/cbdv.202502546) - [Quantum Chemical, Spectroscopic and In Silico (Molecular Docking, Molecular Dynamic and ADME) Studies on Anti-Aging Pentapeptide-3 (Vialox). Akhan D, Bicak B, Kecel Gunduz S, Akalin E, International Journal of Quantum Chemistry, 2025](https://doi.org/10.1002/qua.70085) - [In Vitro and In Silico Assessment of Anticancer Activity of Venom-Derived and Biomimetic Neurotransmitter Inhibitor Pentapeptides. Akhan D, Bicak B, Akman G, Kecel Gunduz S, Cell biochemistry and biophysics, 2026](https://doi.org/10.1007/s12013-026-02095-z) - [Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Errante F, Ledwoń P, Latajka R, Rovero P, et al., Frontiers in chemistry, 2020](https://doi.org/10.3389/fchem.2020.572923) ### Side effects No cytotoxicity in HaCaT keratinocytes up to 1 mg/mL (Akhan et al., 2026). Cytotoxic to some cancer cell lines in vitro, which the authors frame as anticancer potential (Akhan et al., 2026). No animal or human safety data have been published. Commonly reported (anecdotal): mild irritation. ### Storage - Storage: Room temperature, away from light - Lyophilized: 2 years at room temp - Reconstituted: N/A (ready to use) ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured; in silico ADME only (Akhan et al., 2026). Penetration to muscle is unproven - Molecular weight: 495.58 Da - Sequence: Gly-Pro-Arg-Pro-Ala-[NH2] ### Categories - [Cosmetic](https://peptidelabs.app/peptides/category/cosmetic/) - [Anti-Aging](https://peptidelabs.app/peptides/category/anti-aging/) - [Skin Health](https://peptidelabs.app/peptides/category/skin-health/) ## Vilon URL: https://peptidelabs.app/peptides/vilon/ Also known as: KE dipeptide, KE, Lys-Glu Evidence level: Preclinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Khavinson-series synthetic dipeptide KE (Lys-Glu); in rodents it slowed induced bladder tumours but did not extend mouse lifespan, and it reactivated chromatin in lymphocytes from older donors. Vilon is the dipeptide KE (Lys-Glu) from the St. Petersburg Institute of Bioregulation and Gerontology. In rats it inhibited chemically induced bladder tumours (Pliss 2001). In female CBA mice it did not change survival (Anisimov 2001), and in erbB-2/NEU transgenic mice lung metastases were 2.6 times higher than in the Epitalon group (Alimova 2002). Cell work covers chromatin in lymphocytes from older donors (Lezhava 2004) and gene expression in aging mesenchymal stem cells (Ashapkin 2020; Khavinson 2023). Human reports in diabetes patients are uncontrolled (Kuznik 2007). Nearly all work comes from one group. ### Benefits Fewer chemically induced bladder tumours (rat), chromatin reactivation in lymphocytes from older donors (in vitro), gene expression changes in aging mesenchymal stem cells (in vitro); no lifespan extension (mouse) ### Dosing reference - Research dose: 200 to 1000 mcg daily: vendor/community range; not compared with the doses in the uncontrolled human reports - Range: 200 to 1000 mcg, 1x daily Sold as oral capsules and as lyophilized powder for injection. Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules. Doses in the uncontrolled Russian human reports have not been compared with this range. ### Mechanism Proposed, from the developing group. In cultured lymphocytes from older people it was reported to reactivate condensed chromatin (Lezhava 2004). In aging human mesenchymal stem cells it changed gene expression (Ashapkin 2020), including SIRT1, PARP1 and PARP2 (Khavinson 2023). A microarray study found gene expression changes in mouse heart (Anisimov 2002). The old claims about cytokine production and innate and adaptive immunity had no source. ### Evidence Preclinical: animal or in vitro data only - Inhibited development of chemically induced urinary bladder tumours in rats (Pliss et al., 2001) - Did not change survival in female CBA mice, in a study of aging biomarkers and spontaneous tumours (Anisimov et al., 2001) - In erbB-2/NEU transgenic mice, lung metastases were 2.6 times higher than in the Epitalon group (Alimova et al., 2002) - Reactivated chromatin in cultured lymphocytes from old people (Lezhava et al., 2004) - Regulated SIRT1, PARP1 and PARP2 gene expression and protein synthesis in aging human mesenchymal stem cells (Khavinson et al., 2023) - Human-trial status: no randomized trial; uncontrolled Russian reports in diabetes patients of different ages (Kuznik et al., 2007), almost all work from the developing group ### References - [Inhibitory effect of peptide vilon on the development of induced rat urinary bladder tumors in rats. Pliss GB, Mel'nikov AS, Malinin VV, Khavinson VK, Bulletin of Experimental Biology and Medicine, 2001](https://doi.org/10.1023/a:1012354603132) - [Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice. Anisimov VN, Khavinson VK, Mikhalski AI, Yashin AI, Mechanisms of Ageing and Development, 2001](https://doi.org/10.1016/s0047-6374(00)00184-6) - [Effect of Epitalon and Vilon treatment on mammary carcinogenesis in transgenic erbB-2/NEU mice (in Russian). Alimova IN, Bashurin DA, Popovich IG, Zabezhinskiĭ MA, et al., Voprosy Onkologii, 2002](https://pubmed.ncbi.nlm.nih.gov/12101568/) - [Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people. Lezhava T, Khavison V, Monaselidze J, Jokhadze T, et al., Biogerontology, 2004](https://doi.org/10.1023/B:BGEN.0000025070.90330.7f) - [Studies of the effects of Vilon and Epithalon on gene expression in mouse heart using DNA-microarray technology. Anisimov SV, Bokheler KR, Khavinson VKh, Anisimov VN, Bulletin of Experimental Biology and Medicine, 2002](https://doi.org/10.1023/a:1015859322630) - [Effect of vilon on the immunity status and coagulation hemostasis in patients of different age with diabetes mellitus (in Russian). Kuznik BI, Isakova NV, Kliuchereva NN, Maleeva NV, et al., Advances in Gerontology (Uspekhi Gerontologii), 2007](https://pubmed.ncbi.nlm.nih.gov/18306698/) - [Gene expression in human mesenchymal stem cell aging cultures: modulation by short peptides. Ashapkin V, Khavinson V, Shilovsky G, Linkova N, et al., Molecular Biology Reports, 2020](https://doi.org/10.1007/s11033-020-05506-3) - [KE peptide regulates SIRT1, PARP1, PARP2 gene expression and protein synthesis in human mesenchymal stem cells aging (in Russian). Khavinson VK, Linkova NS, Ashapkin VV, Shilovsky GA, et al., Advances in Gerontology (Uspekhi Gerontologii), 2023](https://pubmed.ncbi.nlm.nih.gov/37782636/) ### Side effects No controlled safety study has been published. In erbB-2/NEU transgenic mice, lung metastases were 2.6 times higher than in the Epitalon group (Alimova 2002). Commonly reported (anecdotal): injection-site irritation. ### Storage - Storage: Room temperature - Lyophilized: 24+ months ### Pharmacology - Half-life: No published pharmacokinetic data in any species - Bioavailability: Not measured in any species - Molecular weight: 275.3 Da - Sequence: Lys-Glu ### Categories - [Bioregulator](https://peptidelabs.app/peptides/category/bioregulator/) - [Immune](https://peptidelabs.app/peptides/category/immune/) ## VIP URL: https://peptidelabs.app/peptides/vip/ Also known as: Vasoactive Intestinal Polypeptide, Aviptadil (synthetic form used in trials), VIP-28 Evidence level: Clinical Reviewed: 2026-10-06 (audit-2026-10) ### Overview Vasoactive intestinal peptide, a 28-amino-acid neuropeptide acting at VPAC1 and VPAC2 receptors; studied for vasodilation, immune modulation and neuroprotection. VIP is a 28-residue neuropeptide first isolated from small intestine for its vasodilator activity (Said and Mutt, 1970). Its synthetic form, aviptadil, is what human studies have used. Intravenous infusion in volunteers produced flushing, a faster pulse and a wider blood pressure amplitude, with a plasma half-time of about a minute (Domschke et al., 1978). Inhaled aviptadil gave small, brief pulmonary vasodilation in 20 patients with pulmonary hypertension (Leuchte et al., 2008). Two randomised trials in COVID-19 respiratory failure missed their primary endpoints, the larger one stopped for futility (Youssef et al., 2022; Brown et al., 2023). Aviptadil with phentolamine is used intracavernosally for erectile dysfunction (Al-Mitwalli et al., 2025). The intranasal CIRS protocol it is sold for has no published trial. ### Benefits Vasodilation (human, IV and inhaled); anti-inflammatory and neuroprotective effects in animal and cell models; two randomised trials in COVID-19 respiratory failure missed their endpoints ### Dosing reference - Research dose: 50 to 200 mcg intranasal (community range, no published human dose for this route; trials used 100 mcg inhaled or 600 to 1800 pmol/kg/day intravenously) - Range: 50 to 200 mcg, 1-2x daily - Reconstitution: 2 mL bacteriostatic water - Common vial sizes: 6 mg Published human dosing is inhaled or intravenous, never intranasal or subcutaneous: 100 mcg as a single inhaled dose during right-heart catheterisation (Leuchte et al., 2008), a 3-day intravenous course targeting 600, 1200 and 1800 pmol/kg on successive days (Brown et al., 2023), and graded infusions of 0.6 to 3.3 pmol/kg/min in volunteers (Domschke et al., 1978). The intranasal CIRS protocol the compound is sold for has no published trial. Measured effects of systemic dosing in volunteers were flushing, a faster pulse and a wider blood pressure amplitude. Plasma half-time is about one minute, so effects are brief. ### Mechanism VIP is a 28-residue neuropeptide isolated from small intestine in 1970 as a potent vasodilator (Said and Mutt, 1970). It acts at the VPAC1 and VPAC2 G-protein-coupled receptors and raises cyclic AMP. In healthy volunteers, intravenous infusion reproduced features of the Verner-Morrison syndrome: cutaneous flushing, higher pulse rate, wider blood pressure amplitude and small rises in glucose, free fatty acids and calcium (Domschke et al., 1978). Inhaled aviptadil caused selective pulmonary vasodilation with improved stroke volume and mixed venous oxygen saturation (Leuchte et al., 2008). The rationale tested in COVID-19 was surfactant production and cytokine suppression in alveolar cells (Youssef et al., 2022). Anti-inflammatory and neuroprotective actions are reported in animal and cell models. ### Evidence Clinical: at least one published human trial or an approved drug - Isolated from small intestine as a potent vasodilator peptide (Said and Mutt, 1970) - Graded intravenous infusion in healthy volunteers (0.6 to 3.3 pmol/kg/min) produced flushing, higher pulse rate and wider blood pressure amplitude, with a plasma disappearance half-time of about one minute (Domschke et al., 1978) - A single inhaled 100 mcg dose of aviptadil in 20 patients with pulmonary hypertension gave small, short-lived selective pulmonary vasodilation with no systemic blood pressure effect (Leuchte et al., 2008) - A 196-patient placebo-controlled trial of intravenous aviptadil in critical COVID-19 respiratory failure missed its primary endpoint, with a secondary 60-day survival difference reported (Youssef et al., 2022) - TESICO, 461 patients in the modified intention-to-treat analysis, was stopped for futility: intravenous aviptadil at 600 to 1800 pmol/kg/day over 3 days did not improve the ordinal recovery outcome (Brown et al., 2023) - Human-trial status: aviptadil with phentolamine is used by intracavernosal injection for erectile dysfunction, effective in 59% of 308 referred men in one centre's series, with facial flushing in 22.5% (Al-Mitwalli et al., 2025). openFDA returns no Drugs@FDA application for aviptadil or vasoactive intestinal peptide ### References - [Polypeptide with broad biological activity: isolation from small intestine. Said SI, Mutt V, Science, 1970](https://doi.org/10.1126/science.169.3951.1217) - [Potent peripheral and splanchnic vasodilator peptide from normal gut. Said SI, Mutt V, Nature, 1970](https://doi.org/10.1038/225863a0) - [Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Domschke S, Domschke W, Bloom SR, et al., Gut, 1978](https://doi.org/10.1136/gut.19.11.1049) - [Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Leuchte HH, Baezner C, Baumgartner RA, et al., European Respiratory Journal, 2008](https://doi.org/10.1183/09031936.00050008) - [The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Youssef JG, Lavin P, Schoenfeld DA, et al., Critical Care Medicine, 2022](https://doi.org/10.1097/CCM.0000000000005660) - [Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Brown SM, Barkauskas CE, Grund B, et al., Lancet Respiratory Medicine, 2023](https://doi.org/10.1016/S2213-2600(23)00147-9) - [Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction. Al-Mitwalli A, Holden F, Di Giovanni A, et al., Journal of Sexual Medicine, 2025](https://doi.org/10.1093/jsxmed/qdaf067) ### Side effects In healthy volunteers, intravenous infusion caused cutaneous flushing, a faster pulse and a wider blood pressure amplitude, with small rises in glucose, free fatty acids and calcium (Domschke et al., 1978). Facial flushing occurred in 22.5% of 308 men given aviptadil with phentolamine intracavernosally, and ischaemic priapism in 0.3% (Al-Mitwalli et al., 2025). Inhaled aviptadil caused no side effects in 20 patients and did not lower systemic blood pressure (Leuchte et al., 2008). The COVID-19 trials reported no drug-related serious adverse events (Youssef et al., 2022). There is no safety data for intranasal or subcutaneous use. ### Storage - Storage: Refrigerate 2-8°C (36-46°F) - Lyophilized: 2+ years at room temp, 3+ years refrigerated - Reconstituted: 28-30 days refrigerated ### Pharmacology - Half-life: ~1 min plasma disappearance half-time (human, IV infusion, first-order kinetics; clearance about 9 mL/kg/min; Domschke et al., 1978) - Bioavailability: Not quantified for any route. Human studies used intravenous infusion, inhalation or intracavernosal injection; the apparent volume of distribution on intravenous infusion was about 14 mL/kg with clearance near 9 mL/kg/min (Domschke et al., 1978). No intranasal or subcutaneous data exist. - Molecular weight: 3326.82 Da - Sequence: His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH2 ### Categories - [Immune](https://peptidelabs.app/peptides/category/immune/) - [Neuroprotection](https://peptidelabs.app/peptides/category/neuroprotection/)