KPV: Research Overview

KPV is a tripeptide consisting of the amino acids lysine, proline, and valine (Lys-Pro-Val). It represents the C-terminal three-residue sequence of α-melanocyte-stimulating hormone (α-MSH), a proopiomelanocortin-derived peptide with well-documented anti-inflammatory properties. Research from Luger, Brzoska, and collaborators has shown that KPV retains the anti-inflammatory activity of the full α-MSH molecule — including inhibition of NF-κB signaling and pro-inflammatory cytokine secretion — in a far smaller and more pharmacologically tractable format. Its most-studied application is intestinal inflammation, particularly inflammatory bowel disease models, where its uptake via the intestinal peptide transporter PepT1 gives it a potentially practical oral delivery route. Human clinical data are currently absent from the published literature.

What is KPV?

KPV (H-Lys-Pro-Val-OH) is a tripeptide with a molecular weight of approximately 342.4 Da. It is derived from the C-terminus of α-MSH (positions 11–13) and is sometimes listed under the designation α-MSH(11–13). Unlike the full 13-residue α-MSH, KPV does not carry the N-terminal acetyl group or C-terminal amidation required for high-affinity melanocortin receptor binding, meaning its anti-inflammatory activity operates at least partly through non-melanocortin-receptor pathways. KPV is classified as a research compound with no approved clinical indication and is sold by research-chemical suppliers as lyophilized powder.

Mechanism of Action

At nanomolar concentrations, KPV inhibits activation of NF-κB and MAP kinase inflammatory signaling pathways and reduces downstream secretion of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α. The intestinal dimension of KPV's activity relies on transport via PepT1, a di/tripeptide transporter expressed on intestinal epithelial cells and immune cells in the gut mucosa. Once taken up by PepT1, KPV can act intracellularly to dampen inflammatory signaling. This PepT1-dependent mechanism confers the theoretic possibility of orally targeted delivery to gut tissue — an advantage over full-length anti-inflammatory peptides that are not substrates for this transporter.

What the Research Shows

The anti-inflammatory and immunomodulatory activities of α-MSH-related peptides including KPV were summarized by Brzoska et al. in a landmark review (Ann N Y Acad Sci, 1993) and by Luger et al. (PMC2095288), who established that C-terminal α-MSH fragments retain biological activity. The key mechanistic intestinal paper is Dalmasso et al. (Gastroenterology, 2008; PMID 18061177; PMC2431115), which demonstrated in both cell culture and mouse colitis models (DSS- and TNBS-induced) that KPV is transported by PepT1 and reduces intestinal inflammation — evidenced by decreased pro-inflammatory cytokine expression, reduced inflammatory infiltrates on histology, and accelerated recovery of body weight after DSS challenge. A subsequent study (Didion et al., Inflamm Bowel Dis, 2008; PMID 18022935) confirmed anti-inflammatory potential of KPV in murine IBD models.

More recent work has explored nanoparticle-based oral delivery of KPV to enhance colonic targeting. Vong et al. (PMC5498804) demonstrated that hyaluronic-acid-functionalized nanoparticles loaded with KPV efficiently alleviated experimental ulcerative colitis in mice. All published data remain preclinical; no human clinical trials of KPV for any inflammatory condition have been registered on ClinicalTrials.gov or reported in indexed literature as of 2026. The translation gap between the well-characterized murine IBD models and human therapeutic use has not been bridged.

Reported Dose Ranges

Not medical advice. These are ranges reported in research literature, not personalized recommendations. Consult your physician.

Published dose-finding studies in humans do not exist. All dose data come from animal models (primarily mice) where intraperitoneal, oral, or intracolonic KPV administration was studied at doses that do not translate directly to human equivalents without formal allometric scaling and clinical PK studies. No human dose has been established. Any dosing information circulating outside peer-reviewed literature is not validated by clinical research.

References

Citations for this guide are listed below. All PubMed and PMC links resolve to the NCBI abstract or full-text page for the referenced article.