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 July 2026. FDA reviewers told the July 2026 PCAC that none of the studies they located were in humans.

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2 compounding list in April 2026 (reported effective April 15, 2026, after FDA noted the underlying nominations were withdrawn — removal is not approval and does not by itself authorize compounding). On July 23, 2026 the Pharmacy Compounding Advisory Committee (PCAC) voted 8-6 with 1 abstention to recommend adding KPV to the Section 503A bulk drug substances list, balloting the free base and acetate forms separately with the same result each time; wound healing and inflammatory conditions were the indications under consideration. The FDA's own review team had recommended against inclusion, noting that none of the studies it identified were conducted in humans. PCAC recommendations are advisory and non-binding — the FDA would still need to complete notice-and-comment rulemaking before compounding is authorized.

• —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, and the July 23, 2026 PCAC vote in its favour was an advisory recommendation made over the objection of FDA reviewers, who found no human studies. The substance remains unapproved and under regulatory review.
• ⚠Long-term effects, drug interactions, and effects in pregnancy or specific disease states are uncharacterized in the published literature.