What it is
KPV is the shortest peptide on this site: three amino acids, lysine, proline and valine. It is the tail end of a natural hormone called alpha-melanocyte-stimulating hormone (α-MSH), which is better known for making skin darken but also calms inflammation. Researchers noticed in the 1980s that this three-piece tail kept the anti-inflammatory effect while losing the skin-darkening effect.
Since then KPV has been studied mostly in mice with chemically induced bowel inflammation, where it is given by mouth or by injection, and in cells in a dish. It has never been tested in a human clinical trial. There is no approved medicine containing it, and the FDA has said it has found no human exposure data at all.
KPV (L-lysyl-L-prolyl-L-valine, C16H30N4O4, 342.4 g/mol, CAS 67727-97-3) corresponds to residues 11–13 of α-MSH, the C-terminal tripeptide of the 13-residue melanocortin. Its anti-inflammatory effect in mouse colitis appears to be at least partly independent of the MC1 receptor (Kannengiesser et al., 2008). Proposed mechanisms include inhibition of NF-κB and MAP-kinase signalling and downstream pro-inflammatory cytokine secretion in epithelial and immune cells, and cellular uptake through the intestinal oligopeptide transporter PepT1 (SLC15A1), which is up-regulated in inflamed colon and allows KPV to act inside colonocytes and macrophages (Dalmasso et al., 2008). Interaction with IL-1 receptor signalling has also been proposed. Human pharmacokinetics are unpublished; as a small hydrophilic tripeptide it is expected to be rapidly cleared and susceptible to peptidases, but that has not been measured.
Who made it and when
KPV was not invented so much as noticed. In 1989 Mark Hiltz and James Lipton at the University of Texas Southwestern reported that the last three amino acids of α-MSH were enough to reduce inflammation in animals. Lipton’s group and others in Germany and the United States studied it through the 1990s and 2000s. Two 2008 papers, one from Emory University (Dalmasso and colleagues) and one from Münster (Kannengiesser and colleagues), are the most cited, both in mouse models of inflammatory bowel disease. No pharmaceutical company has taken KPV into human development, and no patent held by a drug developer could be verified.
Hiltz and Lipton (FASEB J 1989) reported that the α-MSH(11-13) tripeptide reduced picryl-chloride-induced ear inflammation in mice. Subsequent work by the Lipton laboratory and by Luger and Brzoska in Münster characterised anti-inflammatory and antimicrobial properties of α-MSH-derived tripeptides, reviewed in Endocrine Reviews in 2008. Dalmasso et al. (Gastroenterology 2008) showed PepT1-dependent uptake and reduced DSS- and TNBS-induced colitis in mice with oral KPV in drinking water; Kannengiesser et al. (Inflamm Bowel Dis 2008) reported benefit in DSS colitis, in CD45RBhi transfer colitis, and in DSS colitis in mice lacking a functional MC1 receptor. Later work packaged KPV in nanoparticles or hydrogels for oral colonic delivery. No IND, sponsor or registered trial exists.
What the data say
Everything comes from animals and cells. In mice given chemicals that inflame the bowel, KPV in the drinking water or by injection reduced weight loss, bleeding and tissue damage. In cell studies it damps the signals that switch on inflammatory genes. Reports of effects on skin wounds, lung inflammation and infection are also animal or laboratory work.
In humans there is nothing: no clinical trial has ever been registered on ClinicalTrials.gov or reported in the literature, so there is no information on effective doses, side effects or safety. When the FDA reviewed KPV in 2023 it said it had found no human exposure data by any route.
Animal data: in DSS colitis, oral KPV (Dalmasso et al. used about 100 µM in drinking water) reduced histological inflammation, myeloperoxidase activity and colonic pro-inflammatory cytokine expression; PepT1 dependence was shown in cell lines, not in PepT1-deficient animals. Kannengiesser et al. reported faster weight regain, reduced inflammatory infiltrate and lower myeloperoxidase activity with KPV in DSS colitis and in CD45RBhi transfer colitis, and KPV rescued MC1R-mutant mice from death during DSS colitis. Other rodent models report reduced inflammation in TNBS colitis, allergic airway disease, uveitis and skin models, and in-vitro antimicrobial activity against Staphylococcus aureus and Candida albicans at micromolar concentrations.
Human data: none. No registered trial (ClinicalTrials.gov query for KPV, Lys-Pro-Val and lysine-proline-valine returns no studies), no pharmacokinetic study, no case series. Adverse effects in humans are therefore unknown rather than absent. This article lists trials as empty on that basis.
Regulatory picture
Approval: no medicine containing KPV is approved anywhere. Compounding: in September 2023 the FDA put KPV in Category 2, the group of substances it said raise significant safety risks, so pharmacies compounding with it could face FDA action; it said it could find no human data. By April 2026 the FDA’s page listed it as withdrawn from that category by its nominator, and in July 2026 an FDA advisory committee, considering it for wound healing and inflammatory conditions, voted narrowly to recommend adding it to the allowed list. That vote does not bind the FDA and no final decision had been published when this was written. Enforcement: no FDA warning letters naming KPV were found.
Approval: none; no IND could be verified.
Compounding: KPV was placed in Category 2 of the interim 503A bulk drug substances policy on 2023-09-29 with FDA stating it “has not identified any human exposure data on drug products containing KPV administered via any route of administration”. FDA’s safety-risk page updated 2026-04-22 lists KPV among substances withdrawn from Category 2 by the nominators. It is not on the 503A bulks list (21 CFR 216.23). On 2026-07-23 the Pharmacy Compounding Advisory Committee reviewed KPV free base and acetate for wound healing and inflammatory conditions and voted narrowly in favour of inclusion; FDA rulemaking is required to give that effect. This article records compounding status as unknown pending that decision.
