KPV

KPV is the C-terminal tripeptide (Lys-Pro-Val, residues 11-13) of alpha-melanocyte-stimulating hormone (alpha-MSH; full sequence SYSMEHFRWGKPV). In preclinical models it is taken up into intestinal epithelial and immune cells by the di/tripeptide transporter PepT1, where it inhibits NF-kB and MAP-kinase signaling and lowers pro-inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 (PubMed 18061177). This activity appears largely independent of melanocortin receptors: KPV does not raise cAMP and retains anti-inflammatory activity in mice with non-functional MC1R (recessive yellow e/e), with effects attributed in part to inhibition of IL-1beta function (PubMed 12750433).

Human evidence

Preclinical only — in vitro (human and rodent cell lines) and rodent models; no registered human clinical trials identified as of June 2026.

Regulatory status

Not FDA-approved for any indication, and not an approved or licensed medicine in any jurisdiction. Removed from the FDA's interim 503A Category 2 compounding list in April 2026 (reported effective April 15, 2026, after FDA noted the underlying nominations were withdrawn — removal is not approval and does not by itself authorize compounding). Scheduled for Pharmacy Compounding Advisory Committee (PCAC) review on July 23, 2026 for possible addition to the 503A bulk drug substances list; PCAC recommendations are advisory and non-binding, with the FDA making any final decision separately.

• —Studied in rodent models of inflammatory bowel disease (DSS- and TNBS-induced colitis) for reduction of intestinal inflammation and pro-inflammatory cytokine expression (PubMed 18061177).
• —Investigated as a melanocortin-derived anti-inflammatory agent acting on NF-kB/MAPK signaling in epithelial and immune cell-culture models (PubMed 18061177, 12750433).
• —Explored preclinically for inflammatory skin and wound-healing contexts, including transdermal/topical delivery research.
• —Examined for receptor-independent anti-inflammatory mechanisms relative to its parent peptide alpha-MSH (PubMed 12750433).

• ⚠No approved human safety profile exists; safety and dosing have not been established in controlled human clinical trials, and reported effects derive from cell and animal studies (PubMed 18061177, 12750433).
• ⚠Because research-grade KPV is sold as an unapproved substance, purity, sterility and endotoxin content are not regulated, and product identity can vary between suppliers.
• ⚠KPV's April 2026 removal from the FDA 503A Category 2 list reflects withdrawn nominations rather than an affirmative safety finding; the substance remains under regulatory review (PCAC, scheduled July 23, 2026).
• ⚠Long-term effects, drug interactions, and effects in pregnancy or specific disease states are uncharacterized in the published literature.