Research index

Neutral one-line summaries with a link to each primary source. Null and negative findings are listed alongside positive ones.

Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH — The originating 1989 report, from the University of Texas Southwestern Medical Center. Graded doses of alpha-MSH (11-13) were compared with saline and a large dose of corticosteroid against picryl-chloride-induced ear swelling in mice; the authors report that alpha-MSH (11-13) inhibited swelling in a dose-related fashion. A single endpoint in one mouse model, and the paper that established the tripeptide as a subject of study at all. source
Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides — The paper that separates the tripeptide from its parent. In mouse crystal-induced peritonitis, systemic KPV, alpha-MSH, the core melanocortin peptide and a MC3/4 agonist each reduced polymorphonuclear leukocyte accumulation, while a selective MC1-R agonist did not; the KPV effect was not blocked by a MC3/4-R antagonist and persisted in mice with a nonfunctional MC1-R. In vitro the results diverged: macrophage activation was inhibited by alpha-MSH and the MC3/4 agonist but not by KPV, and KPV failed to increase cAMP. The authors conclude KPV "is unlikely to mediate its effects through melanocortin receptors". source
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation — The most-cited KPV paper, from Emory University. In human intestinal epithelial cell lines (Caco2-BBE, HT29-Cl.19A) and human Jurkat T cells stimulated with proinflammatory cytokines, the authors report that nanomolar KPV inhibited NF-kappa B and MAP kinase signalling and reduced proinflammatory cytokine secretion, and that uptake was mediated by the di/tripeptide transporter PepT1. KPV added to drinking water reduced the incidence of DSS- and TNBS-induced colitis in mice. Cell lines and mice; the paper's own conclusion is framed as what KPV "might be", not what it is. source
Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease — A mouse study in two colitis models from the University of Muenster. In DSS colitis the authors report earlier recovery, greater regain of body weight, reduced inflammatory infiltrates on histology and reduced colonic myeloperoxidase activity in KPV-treated mice; similar direction in CD45RB-high transfer colitis. In mice expressing a nonfunctional melanocortin-1 receptor, KPV treatment rescued all animals in the treatment group from death during DSS colitis, which the authors read as the effect being at least partly independent of MC1R. Mouse data only. source
Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model — A delivery-system study, and the clearest illustration of why formulation matters here. KPV was loaded into 400 nm nanoparticles encapsulated in an alginate-chitosan hydrogel and given to mice with DSS colitis. The authors report reduced inflammatory and histologic parameters versus DSS alone, and state that by using the nanoparticles KPV could be delivered at a concentration 12,000-fold lower than KPV in free solution for similar effect. The finding belongs to the nanoparticle-hydrogel system as much as to the peptide. source
Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model — A mouse genetics study of the transporter rather than of the peptide. Intestinal PepT1 overexpression increased and PepT1 deletion decreased tumour number, size and inflammation in an AOM/DSS model. KPV prevented carcinogenesis in wild-type mice and, in PepT1-knockout mice, produced none of the effects seen in wild-type animals — which is the study's actual point: the effect tracks the transporter. Mouse models plus human biopsy expression data; no intervention in a person. source
Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis — Another delivery-system study. KPV was loaded into hyaluronic-acid- functionalised polymeric nanoparticles of about 272 nm, encapsulated in a chitosan/alginate hydrogel and given orally to mice. The authors report the functionalised system outperformed the plain KPV-nanoparticle system on mucosal damage and TNF-alpha downregulation. The comparison the paper draws is between two nanoparticle formulations, not between the peptide and nothing. source
Stability-indicating HPLC assay for lysine-proline-valine (KPV) in aqueous solutions and skin homogenates — Analytical chemistry, and the only peer-reviewed handling data for this compound located during data entry. A validated reversed-phase HPLC method reached a limit of detection of 0.01 micrograms per mL and a limit of quantitation of 0.25 micrograms per mL. Under acid, alkali and hydrogen peroxide stress the peptide yielded lys-pro-diketopiperazine as the major degradation product, confirmed by mass spectrometry, and the method separated intact peptide from its degradation products and from endogenous skin-homogenate peaks. source
Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin — The only study in this list performed on human tissue. In dermatomed human cadaver skin, passive diffusion produced KPV permeation below the assay's limit of detection of 0.01 micrograms per mL. Microneedle treatment raised it to 4.4 micrograms per square cm per hour; iontophoresis and iontophoresis with microneedles raised the rate 8-fold and 35-fold over microneedles alone. Confocal imaging showed labelled peptide beyond 100 microns depth. Ex vivo permeation only — nothing was measured in a person. source
Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists — A single-author mechanistic study in an immortalised human bronchial epithelial cell line. The author reports dose-dependent inhibition of NF-kappa B signalling, matrix metalloproteinase-9 activity and IL8 and eotaxin secretion by KPV, and attributes the KPV effect to nuclear import of the peptide, stabilisation of IkappaB-alpha and blocked nuclear translocation of p65RelA, proposing an interaction with the importin-alpha binding site on p65RelA. Contrasted in the same paper with gamma-MSH, whose effect required MC3R. One cell line, one laboratory. source
Structural modification of the tripeptide KPV by reductive "glycoalkylation" of the lysine residue — A negative result, recorded here because this literature seldom reports them. The authors applied a glycomimetic modification to the lysine residue of H-KPV-NH2 and tested the products. Antimicrobial assays "under a variety of conditions, showed no activity for Ac-KPV-NH2 or the alpha- or epsilon-glycoalkylated analogs", although the modified peptides did show stability toward proteolytic enzymes. Note the molecules: this paper works with the C-terminal amide and its acetylated form, not the free acid FDA's table describes. source
Antimicrobial effects of alpha-MSH peptides — The paper usually cited for antimicrobial activity. It gives the parent sequence explicitly as alpha-MSH (1-13), SYSMEHFRWGKPV, and tested both the parent and "its carboxy-terminal tripeptide (11-13, KPV)" against Staphylococcus aureus and Candida albicans, reporting inhibition of colony formation and reduced yeast viability across a broad concentration range, with an effect the authors link to raised cellular cAMP. It is also the source of this file's parent-sequence entry. Read it together with the published comment below. source
Anti-Candida activity of alpha-melanocyte-stimulating hormone (alpha-MSH) peptides — A published comment on the 2000 paper above, with an author reply. Its authors report that they performed microplate-based growth inhibition assays on C. albicans and could not observe any growth-inhibiting effect, and that repeating the original assay with different C. albicans strains gave only a mild effect at 100 micromolar. Read precisely: as abstracted, the experiments described are with alpha-MSH, so this is a failed replication against the parent hormone. It is included because the original paper is routinely cited as KPV evidence. source
Are melanocortin peptides future therapeutics for cutaneous wound healing? — A narrative review by two of the field's principal authors, and useful mainly for what it concedes. It describes truncated alpha-MSH peptides such as KPV as candidates, outlines the in silico, in vitro, ex vivo and animal approaches that would be needed, and offers what its own abstract calls "an unbiased discussion of the pro and contra arguments". Its framing is prospective throughout — these are proposed as future candidates, which is an accurate description of where the evidence stood in 2019 and where, on FDA's 2026 reading, it still stands. source

What the research does not show

There is no human data of any kind. Not a weak trial, not an uncontrolled case series, not a pharmacokinetic sample — nothing. FDA searched the published medical literature, ClinicalTrials.gov, its own adverse event system and its foods complaint system, and states that it did not find information on products containing KPV administered to humans by any route. Everything else on this page is chemistry, regulatory record, or animal and cell-culture work.
No clinical trial of KPV has ever been registered. A query of the ClinicalTrials.gov registry on 2026-09-17 returned a total count of 0 for KPV as an intervention and 0 on a free-text search of the whole registry. There is not a completed trial whose results went unpublished, nor a trial under way; there is no trial. source
The evidence base is preclinical and narrow. FDA's reviewers identified pharmacological studies in in vitro and in vivo models and nothing beyond them, and the published work clusters in two areas: rodent gut inflammation (mouse DSS and TNBS colitis, mouse transfer colitis, mouse colitis-associated tumour models) and inflammation in cultured cells. Cell lines and mouse colitis models are not people with a condition, and a result in one is not a prediction about the other. source
A large share of the animal work does not test KPV on its own; it tests a delivery system carrying KPV, and the delivery system is doing much of the work. Laroui 2010 loaded KPV into 400 nm nanoparticles inside an alginate-chitosan hydrogel and reports that "KPV can be delivered at a concentration that is 12,000-fold lower than that of KPV in free solution, but with similar therapeutic efficacy". Xiao 2017 used hyaluronic-acid- functionalised nanoparticles inside a chitosan/alginate hydrogel and reports that the functionalised system performed better than the plain nanoparticle system. Later papers in this line use self-assembled carrier-free nanodrugs, mucoadhesive hydrogels and cross-linked hydrogels. None of that transfers to the raw peptide, and a result obtained with a nanoparticle is a result about the nanoparticle. source
Route of administration in the published work does not match how this compound is supplied or used. The mouse colitis studies delivered KPV in drinking water or by targeted colonic release. The single nomination FDA evaluated proposed a topical cream or gel. FDA's internet survey found the compound promoted instead as "single-API injectable, oral, topical, and nasal spray drug products". No study exists for any of those routes in a person, and the routes studied in rodents are not the routes being sold. source
The one human-tissue permeation experiment found that unaided permeation was undetectable. In dermatomed human cadaver skin, passive diffusion gave KPV permeation below the assay's detection limit; only microneedle abrasion, iontophoresis, or both together produced measurable transport. FDA reads this both ways, noting it "could limit the systemic bioavailability of KPV applied topically" and equally "could also limit the potential usefulness of KPV as a topical therapeutic agent". A topical product that does not cross the stratum corneum is not a mild version of one that does. source
Much of the literature people cite for KPV is not about KPV. FDA records that of the nine references submitted with the nomination, "eight references are studies on various alpha-MSH ... derivatives conducted in animals" and one concerned skin permeation — none was a study of KPV given to humans. FDA separately excluded from its own evaluation the submitted articles describing N-acetylated KPV and the KPV dimer, as "out of the scope of this evaluation". The parent hormone, the acetylated peptide, the dimer and the tripeptide are four different molecules. source
Where a study has compared the parent hormone with the tripeptide directly, they behaved differently. Getting 2003 reports that macrophage activation, measured as release of KC and interleukin-1 beta, "was inhibited by alpha-MSH and MTII but not by KPV", and that KPV "failed to increase cAMP" where the melanocortin agonist did. Anyone extending an alpha-MSH finding to KPV is extending it across a difference that this paper measured. source
Null results exist and are rarely cited. A 2018 study that modified the lysine residue of the tripeptide reports that antimicrobial assays "under a variety of conditions, showed no activity for Ac-KPV-NH2 or the alpha- or epsilon-glycoalkylated analogs". Separately, a published comment on the 2000 antimicrobial paper reports that its authors repeated the growth inhibition assays and could not observe the effect; as abstracted, the experiments they describe used alpha-MSH rather than the tripeptide, so the failed replication bears on the parent hormone directly and on the tripeptide only by association. source
The mechanism is unknown, which makes the animal findings hard to assess. FDA states that "the molecular targets underlying the pharmacological effects of KPV-related BDSs remain unknown", and that several lines of evidence indicate melanocortin receptors are unlikely to be those targets — KPV did not displace radiolabelled alpha-MSH binding in three preparations, and pharmacological and genetic approaches failed to implicate the MC2, MC3 or MC4 receptors. The proposed alternatives, NF-kappa B inhibition and PepT1-mediated uptake, are proposals in the literature, not established targets. source
There is no toxicology. FDA states that it identified no acute toxicity study, no repeat-dose toxicity study, no genotoxicity study, no developmental or reproductive toxicity study and no carcinogenicity study of either form, and no pharmacokinetic or toxicokinetic study in any species. Unlike BPC-157, where a published preclinical safety package at least exists to argue about, here there is nothing to read. source
The absence of adverse event reports is not a safety finding. FDA retrieved no reports from its adverse event system through December 3, 2025 and no cases from its foods complaint system since 2004 — and states in the same document that reporting is voluntary, that compounders operating under section 503A generally do not report adverse events to FDA, and that it "cannot make definitive conclusions regarding the safety of KPV based on FAERS data alone". An empty database for a substance nobody reports on says nothing. source
FDA considers the substance itself poorly characterised, and the certificates of analysis circulating for it report purity and little else. FDA found no certificate of analysis for the free base in the nomination at all, and states that the ones it found in the literature "only contain purity testing result", with no impurity limits, no aggregate data and no microbiological testing. For the acetate the nominator's certificate gave impurity totals but no identification of any individual impurity. A purity percentage without an impurity profile does not address what FDA names as the concern. source
The naming of this compound does not distinguish the substances being sold. FDA treats KPV (free base) and KPV acetate as different active pharmaceutical ingredients, records that "The CAS number for KPV acetate is the same as that for KPV (free base) in most public references", and lists no UNII code for either. Published work exists on the free acid (H-Lys-Pro-Val-OH), on the amide (H-KPV-NH2) and on the acetylated amide (Ac-KPV-NH2). A figure attached to the name "KPV" in a third-party source cannot be assigned to a specific substance without checking, and the usual identifiers do not settle it. source
The storage and solubility figures published on this site, and on every other site that carries them, trace through FDA's evaluation to supplier product pages and supplier certificates of analysis rather than to a published stability study. They are recorded here because FDA recorded them, with that provenance stated. The one exception is the forced-degradation chemistry, which comes from a peer-reviewed stability-indicating assay and is labelled as such.
Immunogenicity and aggregation have not been assessed for this compound at all. FDA states there is insufficient data to conclude that either form does not present those risks, and notes that peptides as short as two residues have been shown to aggregate. Short does not mean inert.
The anti-doping position is unresolved rather than permissive. No statement from an anti-doping authority naming this compound was retrievable during data entry, and this file does not infer one in either direction from statements about other substances.
The published research does not establish a dose, a route, a schedule, a duration, or a formulation for any use in a person, and it does not establish what happens with long-term use, because no human study of any length has been published.