N-Acetyl Epithalon Amidate
Also known as: Ac-AEDG-NH2, N-Acetyl-Epitalon amidate, Epitalon amidate
Evidence: Preclinical
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
- 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
- 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
- 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
- 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
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