KPV

Evidence grade: C — reviewed September 2026

Controlled human trials: 0 Pilot or open-label human studies: 0 Animal studies: 10+ (mouse and rat, plus in vitro human cell lines)

Also known as: α-MSH(11–13), alpha-MSH C-terminal tripeptide, Lys-Pro-Val Sequence: Lys-Pro-Val (H-Lys-Pro-Val-OH; sold as free base or acetate salt)

One-line rationale: Consistent anti-inflammatory effects across several rodent models and human cell lines, but no human data of any kind, no pharmacokinetics, and no safety studies. The mechanism is still argued over.

What it is

KPV is the last three amino acids of α-melanocyte-stimulating hormone (α-MSH), a 13-amino-acid hormone made in the pituitary and skin. α-MSH does two unrelated things: it darkens pigment through the MC1 receptor, and it dampens inflammation. In 1989 Hiltz and Lipton showed that the tail end of the molecule kept the anti-inflammatory activity while losing the pigment effect. That fragment is KPV.

It is a three-residue peptide with a molecular weight of about 342. It has no approved name, no pharmacopeial monograph, and no UNII code, which becomes relevant in the regulatory section below.

Proposed mechanism

Here is the part most vendor pages get wrong. KPV does not appear to work through the melanocortin receptors that α-MSH uses. It does not displace α-MSH from MC1 receptors in binding assays, does not raise cAMP the way α-MSH does, and still works in mice whose MC1 receptor is non-functional.

Two alternative mechanisms have real support:

NF-κB inhibition. KPV reduces activation of NF-κB, a master switch for inflammatory gene expression, and blunts the downstream effects of IL-1β and TNF-α in cells.
PepT1 transport. In gut epithelial and immune cells, KPV is carried into the cell by PepT1, a di/tripeptide transporter that is normally expressed in the small intestine and becomes upregulated in the inflamed colon. Block PepT1 and the anti-inflammatory effect disappears. This is the leading explanation for why oral KPV does anything in colitis models.

The honest summary: the effect is reproducible, the receptor is unknown.

What the cell and animal evidence shows

Colitis (the strongest line). In two separate labs, KPV reduced weight loss, histological damage, and myeloperoxidase activity in DSS-induced and TNBS-induced colitis in mice, and in a T-cell transfer colitis model. In one study it rescued MC1-receptor-deficient mice from death during DSS colitis. Oral delivery worked, which is unusual for a peptide and is attributed to PepT1.

Skin and wound healing. Rodent studies show faster closure of cutaneous and corneal wounds. The nominated compounding use (a 0.1% topical cream) rests on this line, but a 2017 study on human cadaver skin found KPV barely penetrates the stratum corneum unless the skin is microneedled or driven by iontophoresis.

Neuroinflammation. A single intraperitoneal dose reduced lesion volume and neuronal apoptosis after controlled cortical impact in mice, with reduced microglial activation.

Immune cells. In human neutrophils and macrophage cell lines, KPV and related tripeptides reduce cytokine output, nitric oxide production, and neutrophil migration.

What the human evidence shows

Nothing. Not a trial, not a pilot, not a case series. The FDA’s May 2026 review searched PubMed, Embase, ClinicalTrials.gov, and its own adverse-event databases and found no study of KPV administered to a human by any route, no pharmacokinetic data, and no adverse-event reports. The nominating pharmacy’s own submission cited nine references; eight were animal studies of α-MSH derivatives and one was the cadaver-skin permeation study.

That absence cuts both ways. There are no reported harms because nobody has looked.

Regulatory status

Not approved anywhere. No FDA, EMA, or Japanese Pharmacopeia listing.

KPV was one of six peptides discussed at the FDA’s Pharmacy Compounding Advisory Committee on July 23–24, 2026. FDA staff recommended against adding it to the 503A bulks list, citing inconsistent naming (free base vs. acetate salt sold under the same name), no impurity or aggregation data, and zero human evidence. The committee voted the other way and recommended inclusion. That vote is advisory; FDA has not acted on it, and historically the gap between a recommendation and a final rule has run two years or more. As of this review, compounding pharmacies still cannot lawfully prepare KPV under 503A.

Gaps and caveats

Free base or acetate? Vendors use “KPV” for both. They are different substances with different solubility (0.7 mg/mL vs. 5 mg/mL in water) and the FDA flagged this as a patient-safety issue. Any COA should say which one it is.
Oral data may not generalize. The colitis work leans on PepT1, which is upregulated in an inflamed colon. Whether oral KPV reaches anything useful in a healthy gut, or anywhere past the gut, is unstudied.
Topical data is thin. Poor skin permeation in the one human-tissue study undercuts the cream and gel products being sold.
No toxicology. No acute, repeat-dose, genotoxicity, reproductive, or carcinogenicity studies exist. Short peptides can aggregate and trigger immune responses; nobody has checked.
Degradation. KPV acetate breaks down to a lysine-proline diketopiperazine under acid, base, or oxidative stress. Reconstituted solutions are not stable for long.

Why it’s a C and not a D

The animal literature is not one lab, one model, one paper. It spans four decades, multiple independent groups, and several disease models with the same direction of effect. That is meaningfully more than most compounds at this tier have. It is still entirely preclinical, and until someone runs a human study it stays here.

Key references

Peptide Briefs is an independent reference on peptides as they appear in the scientific literature. Nothing here is medical advice or a recommendation to use any compound.