KPV

Also known as: alpha-MSH (11-13), ACTH (11-13), Lys-Pro-Val, Tripeptide KPV, 67727-97-3

Evidence: Preclinical

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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

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

KPV