What it is
KPV is a short chain of amino acids (a peptide). It has just three: lysine, proline and valine. That makes it the shortest peptide on this site.
KPV is the tail end of a natural hormone called alpha-melanocyte-stimulating hormone (α-MSH). This hormone is best known for darkening the skin. It also calms inflammation (swelling and irritation). In the 1980s, researchers noticed something about this three-piece tail. It kept the effect on inflammation. But it lost the skin-darkening effect.
Since then, KPV has mostly been studied in mice and in cells in a dish. The mice were given chemicals that inflame the bowel. They got KPV by mouth or by injection. KPV has never been tested in a human clinical trial. No approved medicine contains it. The FDA has said it found no data at all on people taking it.
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 Human pharmacokinetics are unpublished; as a small hydrophilic tripeptide it is expected to be rapidly cleared and susceptible to peptidases, but that has not been measured.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
No one really invented KPV. It was noticed. In 1989, Mark Hiltz and James Lipton reported on it. They worked at the University of Texas Southwestern. They found that the last three amino acids of α-MSH were enough to reduce inflammation in animals.
Lipton’s group and others studied it through the 1990s and 2000s. This work took place in Germany and the United States. Two papers from 2008 are the most cited. One came from Emory University (Dalmasso and team). The other came from Münster (Kannengiesser and team). Both studied mice with inflammatory bowel disease.
No drug company has started testing KPV in people. We could not confirm any patent held by a drug company.
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
All the evidence comes from animals and cells. Some mice were given chemicals that inflame the bowel. KPV was given in their drinking water or by injection. In these mice, it reduced weight loss, bleeding and tissue damage. In cell studies, it turned down the signals that switch on genes linked to inflammation. There are also reports about skin wounds, lung inflammation and infection. These too come only from animal or lab work.
In humans there is nothing. No clinical trial has ever been registered on ClinicalTrials.gov. None has been reported in the medical research either. So nothing is known about what dose works, what side effects it has, or whether it is safe. The FDA reviewed KPV in 2023. It said it found no data on people taking it 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 with KPV is approved anywhere.
Compounding (pharmacies mixing their own versions): In September 2023, the FDA put KPV in “Category 2.” This is the group of substances the FDA said raise serious safety risks. Pharmacies that mixed it could face FDA action. The FDA said it could find no human data.
By April 2026, the FDA’s page showed a change. The group that had put KPV forward had withdrawn it from Category 2. In July 2026, a panel that advises the FDA looked at KPV. It was being considered for wound healing and inflammation. The panel voted narrowly in favour of adding it to the allowed list. That vote is only advice. The FDA does not have to follow it. No final decision had been published when this was written.
In October 2026, the US health department (HHS) announced a draft policy. It said it does not intend to take enforcement action against licensed pharmacies or doctors who make single-ingredient KPV products, as long as they follow set conditions, while the FDA writes its final rule. The policy is not binding, and it is not FDA approval. KPV is still not on the official list of allowed ingredients. Comments on the draft are due in mid-November 2026. This page will be updated when a final policy is published.
Enforcement: We found no FDA warning letters that name KPV.
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 restricted.
On 2026-10-30 HHS published a notice of availability of a draft interim Enforcement Discretion Policy (docket HHS-OASH-2026-0496) covering 503A compounding of KPV and five other peptides. HHS states it does not intend to take enforcement action against state-licensed pharmacies, federal facilities or licensed physicians compounding single-active-ingredient products from bulk substance sourced from an FDA-registered manufacturer with a certificate of analysis, dispensed on patient-specific prescriptions with MedWatch adverse-event reporting, pending rulemaking (the list of peptides and these conditions are taken from the Alliance for Pharmacy Compounding’s summary, because the HHS appendices could not be retrieved for this article). The notice says it is not binding and does not add KPV to 21 CFR 216.23; 503B outsourcing facilities and products sold for “research use” are outside it. FDA staff had recommended against listing. Comments are due about 2026-11-13; no final policy had been published when this was written.
