Educational reference. Research use only.
KPV: Mechanism, Research, and Regulatory Status
KPV is the tripeptide Lys-Pro-Val, the C-terminal residues 11-13 of alpha-melanocyte-stimulating hormone, CAS 67727-97-3, molecular weight 342.43 g/mol. No human clinical trials of KPV have been published; the evidence is preclinical (cell lines and mouse colitis models). KPV is not approved by any regulator and is supplied for research use only.
Last reviewed 2026-09-29
What is KPV?
KPV key facts
KPV is the tripeptide Lys-Pro-Val, corresponding to residues 11-13 at the C-terminus of alpha-melanocyte-stimulating hormone, with CAS number 67727-97-3 and a molecular weight of 342.43 g/mol. Unlike the parent hormone, KPV's anti-inflammatory activity in intestinal tissue does not depend on classical melanocortin receptor signalling, and KPV does not reproduce the pigment-producing activity of alpha-MSH. Dalmasso and colleagues reported in Gastroenterology in 2008 that KPV enters intestinal epithelial and immune cells through the PepT1 transporter, and that nanomolar KPV suppressed NF-kappaB and MAP kinase activation, with reduced colitis severity in two mouse models. Kannengiesser and colleagues reported in 2008 that KPV kept its anti-inflammatory effect in MC1R-deficient mice. Viennois and colleagues reported in 2016 that KPV reduced colitis-associated tumors in wild-type mice but not in PepT1-knockout mice. Cutuli and colleagues reported antimicrobial activity of alpha-MSH peptides in 2000. No human trial of KPV is registered or published. KPV is not approved by the FDA, EMA or any comparable regulator and is supplied for research use only.
How does KPV work?
KPV is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone, a sequence it shares with the corresponding region of ACTH. Unlike the parent hormone, its anti-inflammatory activity in intestinal tissue does not depend on classical melanocortin receptor engagement. Dalmasso and colleagues showed that KPV enters intestinal epithelial and immune cells through PepT1, a transporter that pulls short peptides into cells, and that this transport is required for activity.
Once inside the cell, nanomolar KPV suppresses activation of the NF-kappaB and MAP kinase inflammatory signaling cascades. That in turn reduces transcription of pro-inflammatory cytokines including TNF-alpha, IL-6 and IL-8. Genetics support the receptor-independence: KPV kept its anti-inflammatory effect in MC1R-deficient mice, indicating the effect is at least partially independent of MC1R signaling.
Viennois and colleagues then showed the dependence on PepT1 causally. KPV suppressed colitis-associated tumorigenesis in wild-type mice but had no effect in PepT1-knockout mice. Tissue context appears to matter.
In human bronchial epithelial cells, an MC3R-dependent component to KPV's suppression of NF-kappaB-driven signaling has been reported, so the mechanism should not be assumed to be the same across cell types. Separately, alpha-MSH-derived peptides including this C-terminal sequence show direct antimicrobial activity against Staphylococcus aureus and Candida albicans, a property distinct from cytokine modulation. KPV does not reproduce the pigment-producing activity of full-length alpha-MSH.
What has research on KPV found?
What published peer-reviewed research and preclinical studies have established about KPV:
- 01Nanomolar concentrations of KPV inhibited NF-kappaB and MAP kinase activation in intestinal epithelial and immune cell lines, and KPV reduced disease severity in two murine colitis models (Dalmasso 2008).
- 02KPV retained anti-inflammatory activity in MC1R-deficient mice, indicating the effect is at least partially independent of MC1R signaling (Kannengiesser 2008).
- 03KPV prevented tumor formation in a colitis-associated cancer model in wild-type mice but produced no benefit in PepT1-knockout mice, establishing PepT1 as required for the effect (Viennois 2016).
- 04Hyaluronic-acid-functionalized nanoparticles carrying KPV produced greater mucosal protection and TNF-alpha suppression than non-targeted delivery in murine colitis, indicating that free peptide delivery is a limiting factor (Xiao 2017).
- 05Alpha-MSH-derived peptides inhibited S. aureus colony formation and reduced C. albicans viability in vitro, a direct antimicrobial action distinct from cytokine signaling modulation (Cutuli 2000).
- 06No human clinical trial of KPV is registered on ClinicalTrials.gov and no published human interventional study was identified. The efficacy evidence base is entirely in vitro and rodent.
Frequently asked questions about KPV
What is KPV?+
KPV is a synthetic tripeptide with the sequence lysine-proline-valine, corresponding to residues 11-13 of alpha-melanocyte-stimulating hormone. It is used as a research reagent in studies of melanocortin-derived anti-inflammatory signaling and intestinal peptide transport, and is supplied for laboratory research use only.
How does KPV differ mechanistically from full-length alpha-MSH?+
Alpha-MSH acts as an agonist at melanocortin receptors and produces pigmentary effects. The KPV tripeptide, in intestinal models, is instead taken up intracellularly by the PepT1 oligopeptide transporter and inhibits NF-kappaB and MAPK signaling; its activity is retained in MC1R-deficient mice and abolished in PepT1-knockout mice. It does not reproduce the melanogenic activity of the parent hormone.
How does KPV relate to KdPT?+
KdPT (Lys-D-Pro-Thr) is a structurally related synthetic analog studied alongside KPV in the melanocortin literature. It is a different compound with a D-proline and a threonine substitution and should not be treated as interchangeable with KPV in experimental design or in citation of published results.
What is the state of human evidence for KPV?+
There is none identified. No interventional human trial of KPV is registered on ClinicalTrials.gov and no published human study was located. All efficacy findings in the literature derive from cell culture and rodent models, and extrapolation beyond those models is unsupported.
References & sources
Every citation below was resolved against its primary source before publication. Each PMID was checked against its PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.
- [1]Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PMID: 18061177 DOI: 10.1053/j.gastro.2007.10.026
- [2]Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. 2008. PMID: 18092346 DOI: 10.1002/ibd.20334
- [3]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
- [4]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. 2017. PMID: 28143741 DOI: 10.1016/j.ymthe.2016.11.020
- [5]Brzoska T, Luger TA, Maaser C, Abels C, Böhm M. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives. Endocrine Reviews. 2008. PMID: 18612139 DOI: 10.1210/er.2007-0027
- [6]Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of alpha-MSH peptides. Journal of Leukocyte Biology. 2000. PMID: 10670585 DOI: 10.1002/jlb.67.2.233
Where this data comes from
- Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
- Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
- Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes often, so check FDA directly before relying on it.
- Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis. General handling is covered in the storage and stability guide.
Content last reviewed 2026-09-29. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers. It is not medical advice, and it describes no human use.
Is KPV approved for human use?
KPV is not approved by the FDA, EMA, or any comparable regulatory authority for any indication in humans or animals. It has no marketing authorization and no human clinical trial data exist. Compounding status under the FDA 503A bulk drug substances framework has been subject to ongoing review and change; verify against FDA's currently published list rather than any secondary source. Supplied strictly as a research chemical for in vitro and non-clinical laboratory investigation. It is not for human consumption, therapeutic use, veterinary use, or use in any living subject.
Research-use-only material
Specifications and certificate of analysis
KPV is stocked as a research reagent. Analytical documentation, covering identity, purity and the lot-specific certificate of analysis, is published in the certificate library.