KPV Research, Specifications & Scientific Information

Introduction

KPV is three amino acids long: lysine, proline, valine. It is the tail end of α-melanocyte-stimulating hormone, a thirteen-residue peptide whose sequence runs SYSMEHFRWGKPV, and the interest in that tail has a specific origin. α-MSH has well-documented anti-inflammatory activity, but it also acts on melanocortin receptors and produces pigmentary effects, and the literature on the tripeptide begins from the observation that the anti-inflammatory part of the activity appears to survive when almost all of the molecule is cut away and the pigmentary part does not ^[6].

What emerged from following that thread is unusual. The best-characterised handle on KPV is not a receptor but a transporter — PepT1, which carries di- and tripeptides across the intestinal epithelium and is induced in inflamed colon ^[5]. That is a mechanism of delivery rather than of signalling, and it shapes both the research and its limits. The evidence base is entirely preclinical: cultured cells and mice. No clinical trial of KPV is registered or published. This page is a reference record of that literature, with every source resolved against PubMed, Crossref or ClinicalTrials.gov at the time it was built. It describes research, not use, and contains no guidance on handling the material.

What Is KPV?

KPV is a synthetic tripeptide of three standard L-amino acids with free termini and no modification — no acetylation, no amidation, no non-standard residue. PubChem records it as CID 125672 with CAS registry number 67727-97-3 and UNII 7V6LGD8S5R, and lists "MSH (11-13)" among its synonyms, which states its origin precisely: it is residues 11, 12 and 13 of α-melanocyte-stimulating hormone.

It has never been an approved medicine anywhere, and it is not in clinical development. No trial of KPV is registered on ClinicalTrials.gov, and none has been published.

The rationale for studying the tripeptide rather than the parent hormone is set out in the review literature: α-MSH has potent anti-inflammatory and protective effects, and a principal obstacle to using it in inflammatory disorders is its pigmentary action. The C-terminal tripeptide retains the anti-inflammatory effect without that action, and its physicochemical properties and low cost of manufacture were the reasons it was put forward as an alternative ^{[6, 4]}.

Three closely related substances circulate in the same literature and are frequently conflated with KPV. KdPT substitutes D-threonine for the proline and corresponds to residues 193 to 195 of interleukin-1β ^[6]. [Ac-CKPV]2 is a disulfide-linked dimer of an acetylated, cysteine-extended sequence, studied as a candidacidal peptide and with a published three-dimensional structure ^[3]. α-MSH itself is the thirteen-residue parent. Results reported for any of these do not transfer to KPV.

KPV Specifications

KPV is three standard L-amino acids — lysine, proline, valine — with a free N-terminal amine and a free C-terminal carboxylate, and no modification of any kind. PubChem records it as CID 125672 with CAS registry number 67727-97-3 and UNII 7V6LGD8S5R, molecular formula C16H30N4O4 and average mass 342.4 g/mol; the register's synonyms include 'MSH (11-13)', which states the compound's origin exactly. Alpha-melanocyte-stimulating hormone is the thirteen-residue peptide SYSMEHFRWGKPV, and KPV is its last three residues. The catalog record for this laboratory reagent carries the sequence but leaves CAS, formula and mass blank; the values shown above are the register's. Two close relatives appear in the same literature and are different substances: KdPT, in which the proline is replaced by D-threonine and which corresponds to residues 193 to 195 of interleukin-1 beta, and [Ac-CKPV]2, a disulfide-linked dimer of an acetylated cysteine-extended form. Neither is KPV, and results reported for them do not transfer to it.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does KPV Work?

The published account has two halves, and only one of them is about signalling.

The first half is entry. PepT1, the di/tripeptide transporter encoded by SLC15A1, is normally expressed in the small intestine and is induced in the colon during inflammatory bowel disease. KPV is a substrate of it, in immune cells as well as epithelial ones ^[5]. The consequence is a targeting mechanism that has nothing to do with affinity for a signalling receptor: a substrate of an uptake transporter accumulates wherever that transporter is expressed, so induction of PepT1 in inflamed colon concentrates the peptide into the tissue of interest. This is why the rodent work is gastrointestinal rather than systemic.

The second half is what it does once inside: inhibition of NF-κB and MAP kinase inflammatory signalling, with reduced secretion of pro-inflammatory cytokines, at nanomolar concentrations ^[5]. The molecular step between entering the cell and inhibiting those pathways has not been identified. No intracellular binding partner has been reported.

What the account does not contain is melanocortin receptor agonism. That was tested directly and not found, and the detail is in the next section.

KPV Mechanism of Action

In vitro research

Transport and inhibition of inflammatory signalling. Human intestinal epithelial cells (Caco2-BBE and HT29-Cl.19A) and human T cells (Jurkat) were stimulated with pro-inflammatory cytokines in the presence or absence of KPV, with readouts by NF-κB luciferase reporter, Western blot, real-time RT-PCR and ELISA. Nanomolar concentrations inhibited activation of NF-κB and of MAP kinase signalling and reduced pro-inflammatory cytokine secretion. Uptake experiments using unlabelled KPV as a competitor for a radiolabelled PepT1 substrate, and using tritiated KPV to determine uptake kinetics, established that the peptide is transported by PepT1 in both cell types ^[5].

The melanocortin receptor question. In HaCaT keratinocytes and in normal human keratinocytes, no elevation of cyclic AMP was detected in response to α-MSH, to KPV, to KP-D-V or to ACTH peptides — cyclic AMP being the canonical melanocortin-1 receptor readout. Rapid, acute intracellular calcium responses were observed to all of those peptides across 10⁻¹⁵ to 10⁻⁷ M, but only in the presence of an adenosine agonist that inhibits the cyclic AMP pathway ^[2].

That is a specific negative result and it matters for how this compound is described. KPV is derived from a melanocortin ligand; it has not been shown to behave like one. The review literature reflects this by placing the tripeptide's activity outside the melanocortin pharmacophore rather than within it ^[7].

Antimicrobial activity. α-MSH and its C-terminal tripeptide inhibited colony formation by Staphylococcus aureus, reversed the enhancing effect of urokinase on colony formation, and reduced viability and germ tube formation of Candida albicans over a broad range of concentrations. The authors attributed the effect to an increase in cyclic AMP within the organisms, and reported that the peptides did not reduce killing of either pathogen by human neutrophils but enhanced it ^[1].

These are observations in cultured cells and in microbiological assays. They establish nothing about animals or people.

What Is KPV Being Researched For?

The research literature on KPV is narrow and almost entirely gastrointestinal, which follows directly from the transporter that carries it:

• Murine colitis. Models induced by dextran sulfate sodium and by trinitrobenzene sulfonic acid ^[5].
• Colitis-associated tumorigenesis. A model combining azoxymethane with dextran sulfate sodium, in wild-type, PepT1-overexpressing and PepT1 knockout mice ^[8].
• Colon-targeted delivery. Nanoparticle and hydrogel systems built to release the peptide in the colonic lumen ^[9].
• Melanocortin peptide pharmacology. The basic question of how α-MSH-derived fragments act, which is where the keratinocyte signalling work sits ^{[2, 7]}.

The review literature has proposed a wider set of indications — inflammatory skin and bowel disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation, arthritis ^[6] — but those are proposals for future work, published in 2008, and the registered trial landscape has not followed them. There is no human research on KPV, so this page carries no human-clinical section.

Preclinical Research on KPV

Animal research

Colitis models. KPV added to drinking water reduced the incidence of colitis induced by dextran sulfate sodium and by trinitrobenzene sulfonic acid in mice, assessed histologically and by pro-inflammatory cytokine mRNA expression ^[5].

The knockout experiment. In a colitis-associated cancer model, mice overexpressing human PepT1 in intestinal epithelial cells had larger tumours, higher tumour burden and more intestinal inflammation than wild-type animals, while PepT1 knockout mice had significantly fewer and smaller tumours and less inflammation. KPV prevented carcinogenesis in wild-type mice — and produced none of that effect when given to PepT1 knockout mice ^[8].

The knockout arm is what raises this above a correlation. Removing the transporter removed the effect, which is about as direct a demonstration of a delivery mechanism as a rodent experiment can give.

Formulated delivery. KPV loaded into hyaluronic acid-functionalised polymeric nanoparticles of roughly 272 nm diameter and slightly negative zeta potential was delivered to colonic epithelial cells and macrophages. Administered orally inside a chitosan/alginate hydrogel, the formulation reduced mucosal damage and down-regulated TNF-α in a mouse model of ulcerative colitis more effectively than nanoparticles without the hyaluronic acid functionalisation ^[9].

Limitations. These are chemically induced colitis models in mice, which reproduce mucosal inflammation but not the chronic relapsing disease they stand in for. The work comes largely from one laboratory group and its collaborators. The effort that has gone into carrier systems is itself informative: a tripeptide given by mouth is a substrate for the same peptidases that digest dietary protein, and the formulation literature exists because the unformulated molecule does not reliably arrive. Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of KPV Research

In vitro research

The family, and why its members are not interchangeable. The anti-inflammatory tripeptide literature extends beyond KPV to a small set of relatives, and a page that did not separate them would misrepresent all of them. KdPT, with D-threonine in place of proline, corresponds to a sequence in interleukin-1β rather than in α-MSH and has its own reported activity ^[6]. The dimer [Ac-CKPV]2 has been studied specifically as a candidacidal agent, and its three-dimensional structure in solution has been determined ^[3]. The parent hormone α-MSH acts at melanocortin receptors that the tripeptide has not been shown to engage ^[2].

Where the proposals came from. The 2008 Endocrine Reviews survey is the source of most of the broader claims made for this peptide. It reviewed the anti-inflammatory effects of α-MSH validated in animal models — experimentally induced fever, contact dermatitis, vasculitis, fibrosis, ocular, gastrointestinal, brain and airway inflammation, arthritis — and then argued that KPV, having the anti-inflammatory action without the pigmentary one, was a candidate for the same list ^[6]. The animal models in that list were studies of α-MSH. Attributing their results to the tripeptide is a step the review proposed, not a step the data itself supported.

What has not happened since. Eighteen years on, that proposal has not been tested in a registered clinical trial. The absence is the most important single fact about the evidence base for this compound, and no amount of preclinical detail changes it.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

KPV vs Related Compounds

Composition and mechanism only; no comparison of effect is made between these compounds.

Origin

KPV — residues 11 to 13 of α-melanocyte-stimulating hormone. GHK-Cu — a three-residue peptide occurring in plasma and within type I collagen, complexed with copper(II). LL-37 — the 37-residue C-terminal fragment of the human cathelicidin hCAP18. BPC-157 — fifteen residues from a gastric juice fraction.

Route into the cell or onto the target

KPV — carried in by the PepT1 transporter ^[5]. GHK-Cu — coordination of a metal ion, with very poor permeation across intact skin. LL-37 — interaction with bacterial and host membranes, and with several host receptors. BPC-157 — no identified target or transporter.

Melanocortin pharmacology

KPV is derived from a melanocortin ligand but has not been shown to signal through melanocortin-1 receptor cyclic AMP ^[2]. Melanotan II and PT-141 are melanocortin receptor agonists proper and belong to a different pharmacological class despite the shared ancestry.

Evidence shape

KPV — cell culture and mouse colitis models, no registered human trial. GHK-Cu — chemistry and cell culture, one registered trial with no results. LL-37 — extensive in vitro literature plus randomised controlled trials in chronic wounds. None of the four is an approved medicine in the United States, and approval is specific to a compound and an indication.

Chemical & Molecular Characteristics

KPV is about as simple as a peptide gets: Lys-Pro-Val, molecular formula C16H30N4O4, average mass 342.4 g/mol, one free α-amino group at the lysine, one free carboxylate at the valine, and a second free amine on the lysine side chain. There is no acylation, no amidation, no cyclisation and no non-standard residue, so the three-letter string is the complete covalent structure.

Three points follow from that simplicity.

Registers are consistent for this compound. CAS 67727-97-3, PubChem CID 125672 and UNII 7V6LGD8S5R all describe the same free-acid tripeptide, and the formula and mass agree across them. The catalog record for this laboratory reagent carries the sequence but leaves the numerical identifiers blank; the values in the table above are the register's.

The name "KPV" is a sequence, not a molecule. A search for "KPV" in PubChem by name returns 2-oxo-5-phenylpentanoic acid, an unrelated small molecule, because three-letter strings are poor identifiers. The reliable query is "Lys-Pro-Val" or the CAS number. This is a practical point for anyone checking a supplier's identifiers.

Proline in the middle is the interesting position. The central proline is what KdPT replaces with D-threonine, and the substitution changes the molecule's provenance entirely — from a melanocortin fragment to an interleukin-1β fragment ^[6]. A single-residue difference between two tripeptides is a large fraction of the molecule, and it is why the two are not discussed interchangeably here.

Stability. No stability or pharmacokinetic study of KPV has been published in the indexed literature. The absence of modification means there is nothing in the structure to resist aminopeptidase or carboxypeptidase activity, and the extensive carrier-formulation literature built around this peptide ^[9] is the clearest available commentary on that.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Cutuli M, Cristiani S, Lipton JM, et al.. Antimicrobial effects of alpha-MSH peptides Journal of leukocyte biology; 2000. PMID 10670585 doi:10.1002/jlb.67.2.233
2. Elliott RJ, Szabo M, Wagner MJ, et al.. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells The Journal of investigative dermatology; 2004. PMID 15102092 doi:10.1111/j.0022-202X.2004.22404.x
3. Catania A, Grieco P, Randazzo A, et al.. Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [Ac-CKPV]2 The journal of peptide research : official journal of the American Peptide Society; 2005. PMID 15946192 doi:10.1111/j.1399-3011.2005.00265.x
4. Luger TA, Brzoska T. alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs Annals of the rheumatic diseases; 2007. PMID 17934097 doi:10.1136/ard.2007.079780
5. Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al.. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation Gastroenterology; 2008. PMID 18061177 doi:10.1053/j.gastro.2007.10.026
6. Brzoska T, Luger TA, Maaser C, et al.. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases Endocrine reviews; 2008. PMID 18612139 doi:10.1210/er.2007-0027
7. Brzoska T, Böhm M, Lügering A, et al.. Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore Advances in experimental medicine and biology; 2010. PMID 21222263
8. Viennois E, Ingersoll SA, Ayyadurai S, et al.. Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model Cellular and molecular gastroenterology and hepatology; 2016. PMID 27458604 doi:10.1016/j.jcmgh.2016.01.006
9. Xiao B, Xu Z, Viennois E, et al.. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis Molecular therapy : the journal of the American Society of Gene Therapy; 2017. PMID 28143741 doi:10.1016/j.ymthe.2016.11.020

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: KPV specifications and lot documentation