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KPV

Status Not approved for human useBest evidence E4Sources checked 2026-09-17

KPV is a three amino acid fragment of alpha-MSH with anti-inflammatory activity in cell culture and in mice. No human trial of it has ever been published or registered, and the FDA said the same in its own 2026 review.

Identity

Sequence
Lys-Pro-Val (H-Lys-Pro-Val-OH)
Formula
C16H30N4O4
Molar mass
342.44 g/mol
CAS
67727-97-3
PubChem CID
125672

What it is

KPV is a tripeptide: lysine, proline, valine. It is the last three residues of alpha-melanocyte stimulating hormone, a thirteen amino acid hormone, so it also appears in the literature as α-MSH(11–13). Unlike the parent hormone it carries no pigment-inducing activity.

A caution for anyone reading the literature. Several published papers headed “KPV” studied different molecules. A C-terminal amide (H-KPV-NH2), a D-amino-acid analogue used in rat burn work, and a disulfide-linked dimer called (CKPV)2 or CZEN-002 all appear under that name. The dimer is a distinct compound with its own separate human exposure record. Findings from those papers are not KPV findings, and they are routinely cited as though they were.

How it works

Two mechanisms are reasonably well supported in laboratory work, and one widely repeated claim is not.

It suppresses NF-κB

In human intestinal and bronchial epithelial cell lines, nanomolar KPV inhibited NF-κB and MAPK activation and reduced pro-inflammatory cytokine output (Dalmasso 2008). In bronchial epithelium it appeared to enter the nucleus and block p65RelA translocation by competing at the importin-α3 binding site, an action requiring no cell-surface receptor at all (Land 2012).

It enters cells through PepT1

KPV is a substrate of the di/tripeptide transporter PepT1 (SLC15A1), which is low in healthy colon and rises in inflammatory bowel disease. This produced the strongest causal evidence in the whole KPV literature: in PepT1-knockout mice, KPV’s protective effect disappeared entirely (Viennois 2016). That is a genuine mechanistic result. It is also in mice.

The receptor question is unsettled

KPV protected mice with non-functional MC1R from chemically induced colitis, which argues against melanocortin receptor dependence (Kannengiesser 2008). In human keratinocytes it produced no cAMP rise, unlike classic MC1R agonism, though it did mobilise intracellular calcium (Elliott 2004). Reviews commonly state that KPV binds MC1R. No published binding affinity for any melanocortin receptor was located during this source pass.

Research evidence

Human evidence: none

No human trial of KPV has been published. None is registered on ClinicalTrials.gov. Searches covered KPV, Lys-Pro-Val, lysine-proline-valine and CZEN-002 as interventions, and PubMed filtered to clinical trial and randomised controlled trial publication types, returning nothing in every case.

The FDA reached the same conclusion in its own 2026 review, stating there were “no published clinical studies in humans” and “a lack of any human data on drug products containing these substances.” The agency also reported that outsourcing facilities recorded no KPV-containing products between 2017 and 2025, so there is not even an observational compounding record.

One adjacent human study is often cited as if it were KPV. It is not. An open-label phase I/II of CZEN-002, the (CKPV)2 dimer, enrolled twenty women with vulvovaginal candidiasis, seventeen completing. Uncontrolled, company-reported, and a different molecule.

Preclinical evidence

  • Mouse colitis. Reduced colitis incidence and cytokine mRNA in DSS and TNBS models (Dalmasso 2008).
  • Mouse colitis, MC1R-nonfunctional. Faster recovery and reduced histologic infiltrate, retained without working MC1R (Kannengiesser 2008).
  • Mouse colitis-associated cancer. Prevented carcinogenesis in wild-type animals; effect abolished in PepT1-knockouts (Viennois 2016).
  • Rabbit corneal abrasion, topical. Eight of eight corneas re-epithelialised at 60 hours against zero of eight on vehicle, and the effect was blocked by a nitric oxide synthase inhibitor (Bonfiglio 2006). Very small n, acute mechanical injury.
  • Human keratinocytes, in vitro. Restored viability and reduced IL-1β after particulate-matter injury (Sung 2025). Cell culture only.

Every colitis model here is chemically induced. None reproduces how human ulcerative colitis or Crohn’s disease actually arises.

The delivery problem

A large share of the encouraging KPV literature is really evidence that an engineered delivery system works, which most sources covering this compound do not mention.

Nanoparticle-formulated KPV achieved equivalent protection in mice at a concentration twelve thousand times lower than free KPV (Laroui 2009). Across human skin tested outside the body, passive transdermal permeation of KPV fell below the limit of detection and required microneedles or iontophoresis to move at all (Pawar 2017). A 2026 prodrug paper exists specifically because free KPV reaches the colon poorly (Cheng 2026).

Read plainly, that body of work says free KPV is inefficient, and the formulation is doing much of the lifting.

Safety

There is no human safety data of any kind. No pharmacokinetics, no acute or repeat-dose toxicity, no genotoxicity, no developmental or carcinogenicity studies. The FDA specifically flagged immunogenicity and peptide aggregation as unaddressed risks.

Animal and cell studies reported no overt toxicity at the concentrations used, but none of them was designed as a toxicology study.

One signal is worth stating directly. PepT1 overexpression increased tumour burden in the same colitis-associated cancer model in which KPV reduced it (Viennois 2016). KPV went the protective direction, but the transporter it depends on is the same one implicated in tumour promotion.

KPV degrades under acid, alkali and peroxide to lys-pro-diketopiperazine. The biology of that degradation product is uncharacterised.

Regulatory status

Not approved as a drug in any jurisdiction.

In the United States, KPV was nominated for the 503A Bulk Drug Substances list for topical compounding. The FDA’s own reviewers recommended against adding it, citing the absent human data and finding the substance “not well-characterized,” with no impurity, aggregate or microbiological data available. On 23 July 2026 the Pharmacy Compounding Advisory Committee voted eight to six, with one abstention, in favour of adding it, alongside BPC-157 and TB-500.

That vote is advisory and non-binding. Actual listing requires notice-and-comment rulemaking, which has not concluded.

KPV is not named on the WADA 2026 Prohibited List. Its position under the S0 non-approved substances category is unresolved rather than confirmed permitted, and an athlete should treat it that way.

Handling and identity

Worth knowing before anything else: the FDA found that material sold as KPV is not well-characterised, and that the naming used commercially does not follow INN, IUPAC or USAN conventions. The identity of what is being sold under this name is itself uncertain, separately from any question about whether the molecule does anything.

What is not known

Whether KPV does anything in a human being. No trial has asked.

Beyond that: no human pharmacokinetics or bioavailability by any route, no half-life, no toxicology package, and no chronic-use data in any species. No published binding affinity for any melanocortin receptor. No drug-interaction data, despite PepT1 being a major transporter for beta-lactam antibiotics and ACE inhibitors, which makes competition plausible but unstudied. No characterised biology for its main degradation product.

A systemic anti-inflammatory effect has not been established. The strongest findings are local: the gut lumen through PepT1, the corneal surface, and cultured epithelium. Nothing shows a systemic effect after any route in a mammal at characterised exposures.

Finally, the identity of material sold as KPV is uncertain. The FDA found the substance not well-characterised, with no impurity, aggregate or microbiological data.

Doses used in published research

No published study has administered this compound to a human being, so no dose appears in the literature and none has been established.

Amounts above record what a named source reported administering in a study. They are not a recommendation, not a protocol, and not instructions.

Converting a vial and a syringe into a draw volume is a separate, mechanical question from what amount to use. The reconstitution calculator does that arithmetic for peptide, HCG, and HGH vials.

What circulates E5

Figures reported online. Not dosing, not verified, not endorsed.
Reported useRouteAmount reportedFrequencyReported length
Gut inflammationSubcutaneous200 to 500 mcgOnce daily2 to 4 weeks
Gut inflammationOral250 to 500 mcgOnce dailyNot specified
Skin and woundTopicalNo consistent figureNot specifiedNot specified
As part of the KLOW blendSubcutaneousVaries by vendorNot standardisedNot specified

KPV circulates in research-chemical channels mainly for gut inflammation and skin, and as one of four components in the KLOW blend. Those uses do not follow from the published work, which is confined to cell culture, mice and one rabbit eye study.

Protocol material published online for KPV is unusually consistent. Across vendor pages, forum threads and aggregator sites, the same figure appears again and again: 200 to 500 mcg per day, subcutaneous, for a few weeks at a time, sometimes with an oral or topical variant described for gut or skin complaints.

That consistency is worth reading carefully, because it is not agreement between independent observers. The same three references are usually cited beside it, and none of them contains that figure, or any human figure at all. Two are mouse studies, one delivering KPV inside nanoparticles at loadings that do not translate to a vial of free peptide; the third is a review of melanocortin peptides that proposes no dose. The number circulates on its own.

It is recorded here because people searching for KPV will encounter it, and because knowing where a number came from matters more than the number.

Recorded as an observation about what is published elsewhere. No figure here is a dose, a protocol, or a recommendation, and nothing in this section is evidence that any amount is safe or effective.

Sources

  1. Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PMID 18061177
  2. Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008. PMID 18092346
  3. Viennois E, et al. Critical role of PepT1 in colitis-associated tumorigenesis and the effect of KPV. Cell Mol Gastroenterol Hepatol. 2016. PMID 27458604
  4. Laroui H, et al. Nanoparticles enclosed in a hydrogel deliver KPV to the colon at greatly reduced concentration. Gastroenterology. 2009. PMID 19909746
  5. Land SC. Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides. 2012. PMID 22837805
  6. Elliott RJ, et al. Effects of melanocortin-derived tripeptide KPV on human keratinocyte signalling. J Invest Dermatol. 2004. DOI 10.1111/j.0022-202X.2004.22404.x
  7. Bonfiglio V, et al. Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing. Exp Eye Res. 2006. PMID 16965771
  8. Pawar KR, et al. Transdermal delivery of KPV: passive permeation below the limit of detection across human skin. J Pharm Sci. 2017. PMID 28343991
  9. Sung, et al. KPV attenuates particulate-matter-induced damage in human keratinocytes. Tissue Cell. 2025. PMID 40073467
  10. Cheng, et al. Self-immolative prodrug improves colonic accumulation of KPV. Sci Adv. 2026. PMID 41533788
  11. US Food and Drug Administration. Briefing document on KPV free base and KPV acetate for the 503A Bulk Drug Substances List. 2026. FDA PCAC 2026