What Is Kpv?

Overview

KPV (Lys-Pro-Val) is a naturally occurring tripeptide derived from the C-terminal fragment (amino acids 11–13) of alpha-melanocyte-stimulating hormone (α-MSH), a 13-amino acid POMC-derived neuropeptide.[1][2]

Originally characterized by James M. Lipton and Melanie E. Hiltz in 1989, KPV was identified as the specific molecular fragment responsible for the parent hormone's anti-inflammatory and antipyretic activities — the "active message sequence" that retains immunomodulatory and antimicrobial properties while lacking pigment-inducing activity.[7][8]

A critical mechanistic distinction: KPV does not bind melanocortin receptors (MC1R-MC5R) in mammalian cells, does not increase cAMP, and does not induce melanogenesis. Instead, it enters cells via the PepT1 (SLC15A1) oligopeptide transporter — which is notably upregulated in inflamed colonic tissue — enabling targeted delivery to sites of active inflammation.[3][4]

The FDA placed KPV on the Category 2 Bulk Drug Substances list, citing insufficient human exposure data and potential immunogenicity from peptide-related impurities.[5] No large-scale randomized controlled trials have been published; human data is limited to patent case studies (psoriasis, contact dermatitis).[9]