KPV is the tripeptide Lys-Pro-Val, residues 11–13 at the C-terminus of α-MSH. With KP-D-V it is among the smallest sequences reported to prevent inflammation.

Monograph in Tissue-repair & anti-inflammatory peptides

KPV

Lys-Pro-Val, the last three residues of α-melanocyte-stimulating hormone. It calms inflammation in mouse colitis models. No human study of it has been published or registered.

Also called Lys-Pro-Val · alpha-MSH(11-13) · Lysyl-prolyl-valine

Best evidence: Preclinical only

All evidence is from cells and mice. PubMed has no clinical-trial record and ClinicalTrials.gov lists no study; FDA reports no human exposure data.

Not FDA-approved · FDA compounding nomination withdrawn

Residue Editorial Team · updated Oct 19, 2026

What is KPV?

KPV is the tripeptide lysine-proline-valine, residues 11–13 of α-melanocyte-stimulating hormone (α-MSH). In mice, oral KPV reduced experimentally induced colitis, acting after uptake by the PepT1 transporter in intestinal and immune cells11PubMedPepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Dalmasso G et al. Gastroenterology. 2008.. There are no published or registered human studies22TrialClinicalTrials.gov registry search: KPV peptide OR "lysine-proline-valine". 0 registered studies at fetch., and FDA says it has not identified any human exposure data for KPV by any route33FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..

PubMed records: 5310 reviews
Trial publications: 00 tagged RCT
Registered studies: 00 active · 0 phase 3
Molecular weight: 342.43g/mol · PubChem
Evidence grade: DPreclinical only

Key findings

Nanomolar KPV inhibited NF-κB and MAP-kinase inflammatory signaling and cytokine release in cells; oral KPV reduced DSS- and TNBS-induced colitis in mice, via the PepT1 transporter1.
In two mouse colitis models, KPV sped recovery and weight regain and reduced inflammation; it rescued all MC1R-deficient mice from death in DSS colitis44PubMedMelanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Kannengiesser K et al. Inflamm Bowel Dis. 2008..
Its anti-inflammatory effect in mouse peritonitis did not depend on MC1R or MC3/4 receptors, and unlike α-MSH it did not raise cAMP55PubMedDissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. Getting SJ et al. J Pharmacol Exp Ther. 2003..
Hyaluronic-acid nanoparticles delivering KPV orally alleviated ulcerative colitis in mice more effectively than a non-targeted system66PubMedOrally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Xiao B et al. Mol Ther. 2017..
FDA lists KPV among withdrawn compounding nominations: it has not identified any human exposure data and lacks information on whether KPV would cause harm3.

Written by Residue Editorial Team

Reviewed by Residue Editorial Team · source-by-source check, Oct 19, 2026

First published October 19, 2026

Last updated October 19, 2026

Registry data October 19, 2026 · How we grade · Markdown + sources

What is KPV, chemically?

**Identifiers** retrieved from PubChem.
PubChem CID	125672 “Msh (11-13)”
Formula	C16H30N4O4
Molecular weight	342.43 g/mol
CAS (as listed)	67727-97-3
InChIKey	YSPZCHGIWAQVKQ-AVGNSLFASA-N
Length	3 residues
Route in trials	Oral, intraperitoneal or nanoparticle in mice
Mechanism	α-MSH(11–13) tripeptide; anti-inflammatory, taken up via PepT1; largely melanocortin-receptor independent

Hydrophobic
Basic (+)
Gly / Pro / Cys

Figure 1. Residue sequence of KPV (3 positions) as recorded in PubChem CID 125672 — H-Lys-Pro-Val-OH.

What is KPV?

α-Melanocyte-stimulating hormone (α-MSH) signals through the melanocortin-1 receptor and has anti-inflammatory properties77PubMedalpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. Elliott RJ et al. J Invest Dermatol. 2004.. Its last three residues — lysine, proline, valine, or α-MSH(11–13) — form KPV5. With its D-valine variant KP-D-V, it is among the smallest sequences reported to prevent inflammation7. Figure 1 shows the three residues from PubChem88PubChemPubChem compound record: Msh (11-13). C16H30N4O4 · MW 342.43 g/mol..

How is KPV thought to work?

The most cited mechanism comes from a 2008 Gastroenterology paper. At nanomolar concentrations, KPV inhibited activation of NF-κB and MAP-kinase pathways and reduced pro-inflammatory cytokine secretion. It entered cells via PepT1, a peptide transporter expressed by intestinal epithelial and immune cells, which suggested oral activity1.

KPV does not appear to act like a miniature α-MSH. In a mouse peritonitis model, its anti-migratory effect was not blocked by an MC3/4-receptor antagonist and persisted in mice with non-functional MC1R; unlike α-MSH, it did not inhibit macrophage activation or raise cAMP in vitro5. In human keratinocyte lines, KPV triggered calcium signals but no cAMP elevation7.

What have studies found?

Colitis. Oral KPV reduced the incidence of DSS- and TNBS-induced colitis in mice, with lower pro-inflammatory cytokine expression1. A second group found that in DSS colitis KPV led to earlier recovery, stronger weight regain and fewer inflammatory infiltrates; it also helped in T-cell transfer colitis, and rescued all MC1R-deficient mice in its treatment group from death4.

Delivery. Hyaluronic-acid-functionalized nanoparticles (about 272 nm) delivered KPV to colonic epithelial cells and macrophages. Given orally in a hydrogel, they reduced mucosal damage and TNF-α more than a non-targeted nanoparticle system in a mouse ulcerative-colitis model6.

Humans. We found none. The PubMed record contains no publication tagged as a clinical trial99PubMedPubMed search: (KPV[tiab] AND (peptide OR tripeptide OR MSH OR melanocortin)). 53 records at fetch. and ClinicalTrials.gov returns no study for KPV2.

Is KPV FDA-approved?

**Table 1. Regulatory status of KPV in the United States** — from Drugs@FDA (openFDA) and FDA’s bulk-substance compounding categories, as fetched.
Record	Status	Source
FDA approval	No approved application Drugs@FDA returned no application for “KPV”.	openFDA
Compounding: nominated, then withdrawn KPV	Withdrawn nomination FDA still lists its safety concerns: “FDA has not identified any human exposure data on drug products containing KPV administered via any route of administration. FDA lacks important information regarding any safety issues raised by KPV, including whether it would cause harm if administered to humans.”	3

FDA's entry for KPV states that it has not identified any human exposure data on drug products containing KPV by any route, and lacks important information regarding safety issues, including whether KPV would cause harm if administered to humans3.

What is still unknown?

Any human pharmacology — absorption, half-life, safety — is unstudied.
Translation from mouse colitis to people is untested.

What effects has KPV shown, by body system?

Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.

**Table 2.** Research-observed effects of KPV by body system, with the strongest evidence available for each.
System	What was observed	Grade
Gut inflammation (mice)	Reduced colitis severity in DSS, TNBS and transfer-colitis models1,4.	D
Systemic inflammation (mice)	Reduced leukocyte accumulation in crystal- and IL-1β-induced peritonitis5.	D
Skin cells	Calcium signaling in human keratinocyte lines without cAMP elevation7.	D
Human effects	None studied: no PubMed trial records or registered studies9,2.	D

How much research is there on KPV?

Figure 2. PubMed records per publication year matching (KPV[tiab] AND (peptide OR tripeptide OR MSH OR melanocortin)) — 53 in total; peak 7 in 2026. The 2026 bar is year-to-date (hatched). Volume of literature is not evidence of efficacy. Run this query on PubMed.

No studies listing KPV as an intervention were returned by ClinicalTrials.gov at the last fetch.

Figure 3. 0 studies on ClinicalTrials.gov match the registry search KPV peptide OR "lysine-proline-valine". Multi-phase studies are counted at their highest phase.

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Questions readers ask

What is KPV peptide?

KPV is the tripeptide Lys-Pro-Val, residues 11–13 at the C-terminus of α-MSH5. With KP-D-V it is among the smallest sequences reported to prevent inflammation7.

Has KPV been tested in humans?

Not in any study we could find. PubMed returns no clinical-trial publication9, ClinicalTrials.gov returns no registered study2, and FDA states it has not identified any human exposure data3.

How does KPV work?

In cell and mouse studies, KPV entered intestinal and immune cells through the PepT1 transporter and inhibited NF-κB and MAP-kinase signaling1. Its effects appear at least partly independent of the melanocortin-1 receptor4,5.

Is KPV FDA-approved?

No. FDA lists KPV among bulk substances whose compounding nominations were withdrawn and says it lacks important information about whether KPV would cause harm in humans3.

Is KPV the same as α-MSH?

No. α-MSH is a 13-residue hormone that signals through melanocortin receptors and raises cAMP; KPV is its last three residues and, in mouse and cell studies, did not raise cAMP5,7.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

1 PubMed 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.
2 ClinicalTrials.gov ClinicalTrials.gov registry search: KPV peptide OR "lysine-proline-valine". 0 registered studies at fetch.
3 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
4 PubMed Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis 2008. PMID 18092346; doi:10.1002/ibd.20334.
5 PubMed Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther 2003. PMID 12750433; doi:10.1124/jpet.103.051623.
6 PubMed Xiao B, Xu Z, Viennois E, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther 2017. PMID 28143741; doi:10.1016/j.ymthe.2016.11.020.
7 PubMed Elliott RJ, Szabo M, Wagner MJ, et al. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. J Invest Dermatol 2004. PMID 15102092; doi:10.1111/j.0022-202X.2004.22404.x.
8 PubChem PubChem compound record: Msh (11-13). C16H30N4O4 · MW 342.43 g/mol.
9 PubMed PubMed search: (KPV[tiab] AND (peptide OR tripeptide OR MSH OR melanocortin)). 53 records at fetch. PMID kpv.