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Tripeptide (Lys-Pro-Val); C-terminal fragment of alpha-melanocyte-stimulating hormone (alpha-MSH); melanocortin-derived anti-inflammatory peptide

KPV

Investigationalaka Lysine-proline-valine, Lys-Pro-Val, alpha-MSH (11-13), KPV tripeptide

KPV is the C-terminal tripeptide of alpha-MSH that retains much of the parent hormone's anti-inflammatory activity while being more stable. Its evidence base is preclinical (cell and rodent inflammatory-disease models); it is unapproved and, in the US, has been the subject of FDA compounding review.

Mechanism

KPV is reported to enter cells (in the gut partly via the PepT1 di/tripeptide transporter) and inhibit the NF-kappaB pathway, lowering pro-inflammatory cytokines (e.g., TNF-alpha, IL-6) and reactive oxygen species; some activity is also attributed to melanocortin receptors (MC1R/MC3R). These mechanisms are established mainly in vitro and in animal models, not in controlled human studies.

Regulatory Status by Region

  • United States (FDA)Not FDA-approved; was on the 503A Category 2 list, removed April 2026, and scheduled for Pharmacy Compounding Advisory Committee review (July 2026).
  • Australia (TGA)No registered/approved product; an unapproved therapeutic substance.
  • European Union (EMA)No EMA marketing authorisation.
  • WADANot specifically named on the Prohibited List.

Key Studies

  • PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation (Dalmasso et al., Gastroenterology 2008;134(1):166-178; PMCID PMC2431115)
  • Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis (Xiao et al., Theranostics/ACS 2017; PMCID PMC5498804)
  • Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by modulating the MAPK/NF-kappaB pathway (ScienceDirect 2025, article S004081662500117X)

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