KPV

Molecular identity

Sequence

Lys-Pro-Val

Formula

C16H30N4O4

Molecular weight

342.43 g/mol

CAS

67727-97-3

PubChem CID

125672

What it acts on

• Melanocortin receptors (MC1R and the wider MC-R family) — the review cited here states the tripeptide lacks the entire sequence motif required to bind any known melanocortin receptor, and in mice carrying a non-functional MC1R the protective effect in colitis persisted, so the literature treats the action as at least partly MC-R-independent.
• NF-κB-driven inflammatory transcription — the review describes NF-κB activation, adhesion molecules and chemokine receptors as the pathways through which the parent hormone acts, and records significant similarities between that signalling and the anti-inflammatory signalling of the tripeptide.
• Pro-inflammatory cytokine output — in a rat oral-mucositis model IL-1β and TNF-α were significantly suppressed while IL-10 rose; in a mouse colitis model TNF-α was likewise downregulated.
• Neutrophil influx read as myeloperoxidase — colonic MPO activity, the enzymatic marker of neutrophil infiltration, fell significantly in treated mice alongside a histological reduction of inflammatory infiltrate.
• Epithelial repair markers — CK10 and PCNA expression increased in repaired gingival tissue in the rat model, and cell-migration capacity was retained in vitro after formulation into the hydrogel.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   animal modelInflamm Bowel Dis (2008)

   A murine study in two established colitis models — dextran sodium sulfate colitis and CD45RB-hi transfer colitis — with weight loss, colonic histology and myeloperoxidase activity as readouts. Treated animals recovered earlier and regained significantly more body weight, inflammatory infiltrates and colonic MPO fell significantly, and the transfer-colitis arm reproduced the same pattern. A third arm used mice with a non-functional MC1 receptor, in which the treated group survived DSS colitis; that is the entire basis for the mechanistic claim, and the authors phrase it no more strongly than effects that 'seem to be at least partially independent' of MC1R signalling. The work is wholly in mice.

2. 2.
   animal modelBiomater Sci (2021)

   A biomaterials study in which the tripeptide served as model cargo in a thermosensitive PLGA-PEG-PLGA mucoadhesive hydrogel, with epigallocatechin gallate added as adhesion enhancer, tested in a rat model of chemotherapy-induced oral mucositis. The gel adhered to gingival tissue for hours; treated rats recovered food intake and body weight, ulcerated tissue was repaired with higher CK10 and PCNA expression, IL-1β and TNF-α were significantly inhibited while IL-10 rose, and the loaded gel was active against S. aureus and in MRSA-infected gingival ulcers. The peptide's own contribution cannot be isolated in vivo: the authors themselves credit the EGCG component with inherent antibacterial activity, and the in vivo comparisons run between gel formulations rather than peptide against a peptide-free vehicle.

3. 3.
   reviewAdv Exp Med Biol (2010)

   A review of α-MSH-related anti-inflammatory peptides. It sets out the receptor-based mechanism of the parent hormone across the central nervous system, immune cells and resident somatic cells, and the animal models in which it reads as anti-inflammatory, then makes the point that motivates work on the fragment: KPV lacks the entire sequence motif required for binding to any known melanocortin receptor yet retains almost all of the hormone's anti-inflammatory capacity with no pigmentary action. The review states plainly that the exact signalling mechanism used by KPV and related peptides is currently unknown, and frames these tripeptides — including the KPV derivative KdPT — as interesting candidates rather than as established agents.

4. 4.
   animal modelMol Ther (2017)

   A targeted-delivery study in a mouse model of ulcerative colitis. The tripeptide was loaded into hyaluronic-acid-functionalised polymeric nanoparticles — sub-micron, with a slightly negative zeta potential — encapsulated in a chitosan/alginate hydrogel designed to release them in the colonic lumen and reach colonic epithelial cells and macrophages. The particles were reported non-toxic and biocompatible with intestinal cells, and the functionalised system prevented mucosal damage and downregulated TNF-α more strongly than the same peptide in non-targeted nanoparticles, with the authors describing combined mucosal healing and anti-inflammatory effects. The comparison establishes the value of the targeting vehicle rather than of the free peptide, and all endpoints are mouse-model endpoints.

Used in research on