# KPV - Canonical: https://residue.info/c/kpv/ - Also called: Lys-Pro-Val, alpha-MSH(11-13), Lysyl-prolyl-valine - Evidence grade: D (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. - Status: Not FDA-approved · FDA compounding nomination withdrawn - PubChem CID: 125672 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team KPV is the tripeptide lysine-proline-valine, residues 11–13 of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 cells [1]. There are no published or registered human studies [2], and FDA says it has not identified any human exposure data for KPV by any route [3]. ## 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 transporter [1]. (anchor: https://residue.info/c/kpv/#kf-pmid-18061177) - In two mouse colitis models, KPV sped recovery and weight regain and reduced inflammation; it rescued all MC1R-deficient mice from death in DSS colitis [4]. (anchor: https://residue.info/c/kpv/#kf-pmid-18092346) - Its anti-inflammatory effect in mouse peritonitis did not depend on MC1R or MC3/4 receptors, and unlike α-MSH it did not raise cAMP [5]. (anchor: https://residue.info/c/kpv/#kf-pmid-12750433) - Hyaluronic-acid nanoparticles delivering KPV orally alleviated ulcerative colitis in mice more effectively than a non-targeted system [6]. (anchor: https://residue.info/c/kpv/#kf-pmid-28143741) - FDA lists KPV among withdrawn compounding nominations: it has not identified any human exposure data and lacks information on whether KPV would cause harm [3]. (anchor: https://residue.info/c/kpv/#kf-fda-cat2) ## Effects by system - Gut inflammation (mice) (grade D): Reduced colitis severity in DSS, TNBS and transfer-colitis models [1][4]. (anchor: https://residue.info/c/kpv/#effect-gut-inflammation-mice) - Systemic inflammation (mice) (grade D): Reduced leukocyte accumulation in crystal- and IL-1β-induced peritonitis [5]. (anchor: https://residue.info/c/kpv/#effect-systemic-inflammation-mice) - Skin cells (grade D): Calcium signaling in human keratinocyte lines without cAMP elevation [7]. (anchor: https://residue.info/c/kpv/#effect-skin-cells) - Human effects (grade D): None studied: no PubMed trial records or registered studies [8][2]. (anchor: https://residue.info/c/kpv/#effect-human-effects) ## What is KPV? α-Melanocyte-stimulating hormone (α-MSH) signals through the melanocortin-1 receptor and has anti-inflammatory properties [7]. Its last three residues — lysine, proline, valine, or α-MSH(11–13) — form KPV [5]. With its D-valine variant KP-D-V, it is among the smallest sequences reported to prevent inflammation [7]. Figure 1 shows the three residues from PubChem [9]. ## 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 activity [1]. 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 vitro [5]. In human keratinocyte lines, KPV triggered calcium signals but no cAMP elevation [7]. ## What have studies found? **Colitis.** Oral KPV reduced the incidence of DSS- and TNBS-induced colitis in mice, with lower pro-inflammatory cytokine expression [1]. 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 death [4]. **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 model [6]. **Humans.** We found none. The PubMed record contains no publication tagged as a clinical trial [8] and ClinicalTrials.gov returns no study for KPV [2]. 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 humans [3]. ## What is still unknown? - **Any human pharmacology** — absorption, half-life, safety — is unstudied. - **Translation from mouse colitis** to people is untested. ## Frequently asked questions **What is KPV peptide?** KPV is the tripeptide Lys-Pro-Val, residues 11–13 at the C-terminus of α-MSH [5]. With KP-D-V it is among the smallest sequences reported to prevent inflammation [7]. **Has KPV been tested in humans?** Not in any study we could find. PubMed returns no clinical-trial publication [8], ClinicalTrials.gov returns no registered study [2], and FDA states it has not identified any human exposure data [3]. **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 signaling [1]. Its effects appear at least partly independent of the melanocortin-1 receptor [4][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 humans [3]. **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 cAMP [5][7]. ## Sources [1] PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Dalmasso G et al. Gastroenterology. 2008. https://pubmed.ncbi.nlm.nih.gov/18061177/ [2] ClinicalTrials.gov registry search: KPV peptide OR "lysine-proline-valine". 0 registered studies at fetch. https://clinicaltrials.gov/search?intr=KPV%20peptide%20OR%20%22lysine-proline-valine%22 [3] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [4] Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Kannengiesser K et al. Inflamm Bowel Dis. 2008. https://pubmed.ncbi.nlm.nih.gov/18092346/ [5] Dissection 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. https://pubmed.ncbi.nlm.nih.gov/12750433/ [6] Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Xiao B et al. Mol Ther. 2017. https://pubmed.ncbi.nlm.nih.gov/28143741/ [7] alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. Elliott RJ et al. J Invest Dermatol. 2004. https://pubmed.ncbi.nlm.nih.gov/15102092/ [8] PubMed search: (KPV[tiab] AND (peptide OR tripeptide OR MSH OR melanocortin)). 53 records at fetch. https://pubmed.ncbi.nlm.nih.gov/?term=(KPV%5Btiab%5D%20AND%20(peptide%20OR%20tripeptide%20OR%20MSH%20OR%20melanocortin)) [9] PubChem compound record: Msh (11-13). C16H30N4O4 · MW 342.43 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/125672 --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.