KPV (Lys-Pro-Val)

What Is KPV?

KPV is a three-amino-acid peptide, Lys-Pro-Val, that matches the C-terminal end (residues 11 to 13) of the hormone alpha-MSH and is studied for anti-inflammatory activity. Researchers describe alpha-MSH and certain fragments, including KPV, as modulators of inflammation.^[1]

KPV is one of the carboxyl-terminal tripeptides of alpha-MSH, together with its D-valine analog KP-D-V, that have been reported as the smallest minimal sequences able to prevent inflammation.^[2] Later papers describe it as a naturally occurring or endogenous tripeptide derived from alpha-MSH.^[3][4]

Most published KPV research concerns intestinal inflammation. Studies in mouse and rat colitis models, and in human intestinal and immune cell lines, form the core of the literature, with newer work on drug-delivery hydrogels and nanoparticles that carry KPV to inflamed tissue.^[5][6]

Chemical Structure and Molecular Identity

KPV is the linear tripeptide L-lysyl-L-prolyl-L-valine, with a free amino terminus and a free carboxylic acid terminus. PubChem lists it under CID 125672 with the molecular formula C16H30N4O4 and a molecular weight of 342.43 g/mol. Its CAS number is 67727-97-3, and synonyms include alpha-MSH (11-13) and ACTH (11-13).

The three residues give KPV a simple chemical profile:

• Lysine (K): a basic side chain that carries a positive charge at physiological pH
• Proline (P): a cyclic residue that restricts backbone flexibility
• Valine (V): a branched hydrophobic residue at the C-terminus

At neutral pH the free tripeptide carries a net charge of about +1: the lysine side chain and N-terminal amine are protonated, offset by the C-terminal carboxylate.

Because the same sequence also forms residues 11 to 13 of adrenocorticotropic hormone (ACTH), the fragment is sometimes labeled ACTH (11-13). Its small size makes it a substrate for PepT1, the intestinal di- and tripeptide transporter.^[5]

KPV in solution is unstable under some experimental conditions. A 2021 rat study reported that KPV in solution was very unstable after delivery to the colon, which motivated hydrogel formulations designed to protect it.^[7]

Research History and Development

KPV emerged from research on the anti-inflammatory hormone alpha-MSH and was later developed as a stand-alone tripeptide for intestinal inflammation research. By 2000, reviews described alpha-MSH as an ancient neuroimmunomodulatory peptide and noted that KPV shared its ability to modulate inflammation.^[1]

Early host-defense work found that alpha-MSH and KPV inhibited the bacterium Staphylococcus aureus and the yeast Candida albicans in antimicrobial tests.^[8] A 2004 study then examined how KPV signals in human keratinocytes, asking whether these minimal sequences act through MC1R or through cyclic AMP, the pathway credited with alpha-MSH’s anti-inflammatory effects.^[2]

In 2008, two studies established KPV in colitis research. One showed that KPV enters intestinal epithelial and immune cells through PepT1,^[5] and the other found anti-inflammatory effects in two mouse colitis models, including in mice lacking a functional melanocortin-1 receptor.^[6]

Since 2017, work has focused on delivery systems: hyaluronic acid-functionalized nanoparticles, mucoadhesive hydrogels and PepT1-targeted nanoparticles.^[3][9][10] Reviews in 2025 listed KPV among host-defense peptides of interest for inflammatory bowel disease and among tripeptides studied in wound healing.^[11][12]

Mechanisms Studied in Research

The best-documented mechanism is PepT1-mediated uptake of KPV into cells followed by inhibition of NF-kB and MAP kinase inflammatory signaling. In human intestinal epithelial cells (Caco2-BBE and HT29-Cl.19A) and Jurkat T cells stimulated with proinflammatory cytokines, nanomolar concentrations of KPV reduced NF-kB and MAP kinase activation and lowered proinflammatory cytokine secretion, and uptake depended on PepT1.^[5]

Melanocortin receptor role

The parent hormone alpha-MSH acts through melanocortin receptors and inhibits NF-kB by preserving its inhibitor IkB-alpha.^[1] KPV’s relationship to these receptors is less clear. In human keratinocytes, neither alpha-MSH nor KPV raised cyclic AMP, but both triggered rapid intracellular calcium signals, and KPV raised calcium in hamster ovary cells engineered to express MC1R.^[2] In mice lacking functional MC1R, KPV still protected against colitis, suggesting effects at least partly independent of MC1R.^[6]

Oxidative stress and lipid signaling

In HepG2 liver cells exposed to oleic acid, KPV reduced reactive oxygen species, ERK activation, AKT and mTORC1 phosphorylation and fatty acid synthase expression, and altered PPAR-gamma phosphorylation.^[4] In a rat colitis study, the effect of a KPV-loaded hydrogel was associated with inhibition of oxidative stress.^[9]

Key Findings From Published Studies

KPV has shown anti-inflammatory and tissue-repair effects in rodent colitis and oral mucositis models and in cell culture, but no human clinical trial appears in the indexed literature. Key results by model:

Colitis models

In mouse DSS and transfer colitis models, KPV treatment led to recovery and reduced histological inflammation.^[6] In a mouse model of acute severe ulcerative colitis, KPV served as a PepT1-targeting ligand on cyclosporine A nanoparticles; notably, the nanoparticles without cyclosporine A also showed marked therapeutic effects.^[10] In the 2017 hyaluronic acid study, the roughly 272 nm nanoparticles delivered KPV to colonic epithelial cells and macrophages and appeared nontoxic and biocompatible with intestinal cells.^[3] A 2022 double-network hydrogel carried a negative charge that let it adhere specifically to inflamed rather than healthy colonic mucosa in rats, and it helped KPV retain bioactivity longer under high-temperature conditions.^[9]

Antimicrobial and wound-healing data

KPV inhibited Staphylococcus aureus and Candida albicans in early in-vitro tests.^[8] A KPV hydrogel for oral mucositis showed strong antibacterial activity against S. aureus and preserved KPV’s anti-inflammatory and cell-migration activity. In rats, the treated ulcerated gingiva showed repair with increased CK10 and PCNA expression.^[13] A 2025 review reports that KPV-loaded hydrogels reduced inflammation, promoted tissue regeneration and combated MRSA infections in wound studies.^[12]

Liver cell data

In an oleic acid model of hepatocellular steatosis in HepG2 cells, KPV reduced lipid accumulation without cytotoxicity.^[4]

Because KPV is a tripeptide that can be confused with analogs such as KP-D-V, researchers verify identity with HPLC and mass spectrometry certificates of analysis.

Regulatory and Research Status

KPV is not approved by the US Food and Drug Administration for any use. It remains a research compound.

All indexed studies are in-vitro experiments or rodent models, plus reviews. Authors of the 2008 colitis studies proposed KPV as a possible new agent for inflammatory bowel disease, and a 2025 review grouped it with other host-defense peptides as candidates for that field, but no human efficacy or safety data were found.^[5][11]

Much current work addresses formulation rather than the peptide itself, because KPV’s stability and targeting limit its use in experimental models. Hydrogel and nanoparticle carriers are designed to protect it, keep it at inflamed tissue and deliver it into colonic epithelial cells and macrophages.^[7][3] Because many studies tested KPV inside a carrier, their results reflect the combined system rather than the free peptide alone. In one case, KPV-targeted nanoparticles showed therapeutic effects even without their cyclosporine A payload.^[10]