KPV
Three amino acids from the tail of α-MSH: anti-inflammatory in mouse colitis and cell studies, never given to a person in a published study, and recommended for compounding by FDA's advisers in July 2026.
KPV is lysine-proline-valine, the last three amino acids of α-melanocyte-stimulating hormone. In mice it eased chemically induced colitis whether given in drinking water, in nanoparticles or in gels, and in cell studies it damped NF-κB, the master switch of inflammation. No published study has tested it in people, which is also what FDA told its advisory committee.
What is it?
KPV is the smallest piece of α-melanocyte-stimulating hormone (α-MSH) that still behaves like the parent in some respects. α-MSH was known in the early 1980s to lower fever, and in 1984 researchers found that the tripeptide from its tail, lysine-proline-valine, did too in feverish rabbits, though far less potently. That made KPV a candidate anti-inflammatory that might keep some of α-MSH's benefits without being a full hormone.
The work that put KPV on today's peptide lists came from inflammatory bowel disease research in 2008. Two groups showed it eased colitis in mice: one found it enters gut and immune cells through PepT1, a peptide transporter that the inflamed colon switches on, and the other found it worked even in mice without a functioning MC1R, the receptor α-MSH acts through. Later teams packed it into nanoparticles and gels to protect it from breaking down on the way to the colon, and a 2016 study found it prevented colitis-associated tumours in mice, but only when PepT1 was present.
Outside the gut, cell studies report that KPV blocks NF-κB signalling in airway and skin cells, that it cannot cross intact human skin on its own, and, in a 2026 study, that it slowed fat-cell formation in culture and weight gain in mice on a high-fat diet. How it works is not settled: it did not raise cAMP, the messenger α-MSH uses, and one study traced its effect to the machinery that carries NF-κB into the cell nucleus.
What is missing is any human study. When FDA reviewed KPV for its Pharmacy Compounding Advisory Committee in 2026 it said it could not locate information on KPV's use in humans, and it proposed not adding it to the compounding list. On July 23, 2026 the committee voted to recommend it anyway; FDA had not acted on that vote as of September 27, 2026, and KPV remains unapproved everywhere.
Mechanism of Action
KPV's anti-inflammatory effect seems to work differently from α-MSH's. It gets into cells through the peptide transporter PepT1 and suppresses NF-κB, and in the studies here it did not need the melanocortin receptors α-MSH relies on.
Every step is laboratory or mouse work. No study has given KPV to a person, and even in the lab it barely crosses skin without microneedles or electric current.
Each step is tagged with where it was shown. A dashed red arrow marks a link the evidence does not establish.
The pathway in words
- KPV. Lys-Pro-Val, the C-terminal tripeptide of alpha-melanocyte-stimulating hormone. Shown in: lab. Source: PubMed 28343991.
- Into cells, NF-kB down. In human gut epithelial cells and T cells it entered through the PepT1 transporter and, at nanomolar levels, blocked NF-kB and MAP kinase signalling. Shown in: cells. Source: PubMed 18061177.
- Not the usual receptor. In mouse peritonitis it reduced neutrophil build-up without raising cAMP, and still worked in mice with a nonfunctional MC1R. Shown in: animals. Source: PubMed 12750433.
- Less colitis in mice. Given in drinking water, it reduced the severity of chemically induced colitis in mice, with lower inflammatory markers. Shown in: animals. Source: PubMed 18061177.
- never tested in people. In people. No study has given KPV to people; across human skin in the lab it did not pass without microneedles or iontophoresis. Shown in: lab. Source: PubMed 28343991.
Enters cells through PepT1
In human gut epithelial and T cells, KPV was taken up by PepT1, the di- and tripeptide transporter that is induced in the colon during inflammatory bowel disease. In mice lacking PepT1, KPV no longer prevented colitis-associated tumours.
NF-κB and MAP kinases
Nanomolar KPV blocked NF-κB and MAP kinase activation and cut inflammatory cytokines in gut cells. In airway cells it entered the nucleus and appeared to block the importin binding site on NF-κB's p65 subunit, keeping it out of the nucleus.
Not through melanocortin receptors
It still reduced inflammation in mice with a nonfunctional MC1R, an MC3/4 receptor blocker did not stop it, and it did not raise cAMP in macrophages or keratinocytes. In cells engineered to carry MC1R it did raise calcium, so a receptor role cannot be ruled out entirely.
Oxidative stress
In skin cells exposed to fine dust and in fat-cell precursors, KPV lowered reactive oxygen species and downstream inflammatory or growth signals. These are cell-culture findings, with one mouse diet study behind the fat-cell result.
Published Research
Our evidence set holds 25 papers that name KPV; 14 name it in their titles and have an abstract, and all 14 are carded below: 8 animal studies and 6 laboratory studies, none in people. Nine of the fourteen were added by hand after a title search, because 'KPV' is also an abbreviation in unrelated fields and the automatic search ranked those papers first. Most of the evidence is about the gut, and several of the newer studies are as much about drug-delivery materials as about KPV itself.
Fever in rabbits
Rabbits made feverish with leukocytic pyrogen were given lysine-proline-valine into the brain (0.5 to 2.0 mg) or into a vein (2 to 200 mg). Both routes reduced fever, but less potently than the parent α-MSH, so the authors concluded other parts of α-MSH are needed for its full antipyretic effect.
Peritonitis in mice
In crystal-induced peritonitis, systemic KPV reduced neutrophil build-up, as α-MSH did. Unlike α-MSH it did not inhibit macrophage cytokine release or raise cAMP, an MC3/4 receptor antagonist did not block it, and it still worked in mice with a nonfunctional MC1R and in IL-1β-induced peritonitis. The authors concluded it acts by inhibiting IL-1β, not through melanocortin receptors.
Signalling in human keratinocytes
Neither α-MSH, KPV nor ACTH raised cAMP in HaCaT or normal human keratinocytes. KPV did raise intracellular calcium, but only when the cAMP pathway was inhibited, and in hamster cells engineered to express MC1R both α-MSH and KPV raised calcium.
PepT1 uptake and colitis in mice
In human gut epithelial cells and T cells, nanomolar KPV blocked NF-κB and MAP kinase signalling and reduced inflammatory cytokines, and uptake studies showed it enters through PepT1. Given in drinking water, KPV reduced the severity of DSS- and TNBS-induced colitis in mice, with lower inflammatory cytokine expression.
Two colitis models in mice
In DSS colitis, KPV-treated mice recovered earlier and regained more weight, with fewer inflammatory infiltrates and lower myeloperoxidase activity; in T-cell transfer colitis it also led to recovery. In mice with a nonfunctional MC1R, KPV rescued every treated animal from death during DSS colitis, so its effect is at least partly independent of MC1R.
Human airway epithelial cells
In immortalised human bronchial epithelial cells stimulated with TNF-α or respiratory syncytial virus, KPV dose-dependently inhibited NF-κB, MMP-9 activity and the chemokines IL-8 and eotaxin. It entered the nucleus and competed at the importin-α3 binding site of the p65 subunit, while γ-MSH, compared alongside, needed the MC3 receptor.
Stability assay
A validated HPLC method measured KPV in solution and skin homogenate down to 0.01 µg/mL. Under acid, alkali and peroxide stress KPV broke down mainly into lysyl-proline diketopiperazine, which is relevant to how long an unrefrigerated solution stays what it says it is.
Colitis-associated cancer in mice
Mice overexpressing human PepT1 in the gut developed more and larger colitis-associated tumours, and PepT1-knockout mice fewer; colorectal cancer biopsies showed raised PepT1. KPV prevented tumour formation in normal mice but had no effect in PepT1-knockout mice, showing its effect depends on the transporter.
Oral nanoparticles for colitis
KPV loaded into hyaluronic-acid-coated nanoparticles (about 272 nm) reached colonic epithelial cells and macrophages and was non-toxic to gut cells. Given by mouth in a chitosan-alginate hydrogel, the particles protected the mucosa and lowered TNF-α in mouse ulcerative colitis better than particles without the coating.
Delivery across human skin
Across dermatomed human skin in the laboratory, KPV did not permeate detectably by passive diffusion. Microneedles raised permeation to 4.4 µg/cm²/h, iontophoresis raised it 8-fold over microneedles alone and the two combined 35-fold, and labelled KPV reached below 100 µm into the epidermis.
Rectal hydrogel in rat colitis
KPV in solution is unstable when given rectally. Held in a self-cross-linked polyglutamic-acid hydrogel it was released slowly, kept its anti-inflammatory and cell-migration activity after two hours at body temperature, and improved TNBS-induced colitis in rats more than KPV alone.
Mucosa-targeting hydrogel in rat colitis
A negatively charged double-network hydrogel stuck selectively to inflamed colon lining in rats with TNBS colitis and held KPV there. Given into the colon, the combination improved colitis more than KPV alone, restored the epithelial barrier and shifted gut bacteria toward beneficial species, with reduced oxidative stress.
Skin cells and fine dust
In human HaCaT keratinocytes damaged by fine particulate matter (PM10), 50 µg/mL KPV restored cell viability and cut IL-1β. It lowered reactive oxygen species, ERK and p38 activation, apoptosis markers, NF-κB and caspase-1 activation, and reduced inflammatory cell death in a three-dimensional skin model.
Fat cells and high-fat diet in mice
In 3T3-L1 fat-cell precursors, 100 µg/mL KPV cut lipid staining by about 55% and triglycerides by about 38%, lowering PPARγ and fatty acid synthase through reduced reactive oxygen species and AKT/mTOR signalling. In mice on a high-fat diet, KPV by mouth reduced weight gain, fat tissue, liver mass and cholesterol.
What people say, and what was measured
KPV is three amino acids from the tail of alpha-MSH, sold as an anti-inflammatory for gut and skin. The laboratory case is coherent and specific. Nobody has given it to a person in a published study.
It calms gut inflammation, which is why it is taken for IBD and leaky gut.
Heard in: Grey Peptides listing review, October 1, 2026: listings sell it for gut inflammation and IBD. Sellers are not named.
In mice and in cells. KPV is carried into intestinal and immune cells by the PepT1 transporter and reduced intestinal inflammation there; it had anti-inflammatory effects in two mouse models of colitis; and in a colitis-associated cancer model PepT1 was what delivered the benefit. There is no human trial. PMID: 18061177, 18092346, 27458604
Shown in animals or cells onlyIt is alpha-MSH's anti-inflammatory action without the tanning.
Heard in: Journal of Leukocyte Biology, the dissection of the anti-inflammatory effect of alpha-MSH's core and C-terminal KPV sequence, which the claim traces to (read October 1, 2026). Source
This is the one claim with a real foundation: the anti-inflammatory activity of alpha-MSH was dissected and the C-terminal KPV fragment carries part of it, work done in laboratory models. The comparison of alpha-MSH, KPV and ACTH on inflammation is also laboratory work, and an older study tested KPV on fever in rabbits. PMID: 12750433, 15102092, 6333677
Shown in animals or cells onlyInjecting it or taking it orally delivers it where it is needed.
Heard in: Grey Peptides listing review, October 1, 2026: listings sell injectable vials and capsules. Sellers are not named.
Delivery is the open problem, not a solved one. The published work builds vehicles to get KPV where it is wanted: hyaluronic-acid nanoparticles for oral targeting, a hydrogel that binds it, a cross-linked hydrogel to stabilise it, and iontophoresis across skin pre-treated with micropores. Each of those exists because plain KPV does not get there. PMID: 28143741, 35245681, 34547895, 28343991
Never tested in peopleIt is stable, so a reconstituted vial keeps.
Heard in: Grey Peptides listing review, October 1, 2026: listings give storage advice for reconstituted KPV. Sellers are not named.
A stability-indicating assay was developed precisely because the question needed answering, measuring KPV in aqueous solution and formulations. That is a method paper, not a shelf-life claim for a vial reconstituted at home. PMID: 25298219
Measured, never givenEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
KPV has no approved dose and no human dose from any study. Animal studies gave it in drinking water, by injection, rectally in gels or by mouth in nanoparticles, and the doses were chosen for rodents; the one dose range in a mammal outside rodents is the 1984 rabbit fever study.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full KPV dosage guide — the community figures, why no study supplies a human dose, and what the animal routes do and do not tell you
→ Blend & Stack Calculator — KPV is also sold in multi-peptide vials; the calculator shows what each draw delivers of every component; our blends and stacks hub sets out what each mix contains and what has been studied.
Side Effects & Contraindications
Reported Side Effects
No human safety data exist. These are the only safety-relevant findings in the studies above.
Contraindications & Cautions
With no human trials, no one has defined who should avoid KPV. These cautions follow from what the studies measured.
Legal Status
KPV is not approved as a medicine anywhere. In the United States its compounding status changed twice in 2026 and is still unresolved.
Frequently Asked Questions
?Has KPV been tested in humans?
Not in any published study we could find, and FDA told its advisory committee in 2026 that it could not locate information on KPV's use in humans. The human cells and skin in the studies above were laboratory samples, not people.
?Is KPV approved now that the PCAC recommended it?
No. The committee's July 23, 2026 vote (8–6, one abstention) is advice. FDA had not acted on it as of September 27, 2026, and adding a substance to the 503A list takes rulemaking, so KPV still cannot be compounded.
?Does KPV work by mouth?
In mice it did: in drinking water, and better when protected in nanoparticles or gels, because it enters gut cells through the PepT1 transporter that inflammation switches on. Whether enough survives digestion to matter in a person has not been studied.
?Is KPV the same as α-MSH?
No. It is α-MSH's last three amino acids. It shares some anti-inflammatory activity but, in the studies here, did not use the cAMP signalling α-MSH relies on and worked in mice without a functioning MC1R. Whether it avoids α-MSH's tanning effect has not been measured in our evidence set.
?Can KPV go through the skin?
Not on its own: passive permeation across human skin was below detection in a 2017 laboratory study. Microneedles and a small electric current (iontophoresis) together raised delivery many-fold.
?Why did FDA staff propose against KPV?
Its briefing for the July 2026 meeting said it could find no information on the use of KPV in humans, so it could not reach a conclusion on safety or effectiveness. The committee voted to recommend it regardless.
References
- [Animal] Richards DB, et al. "Effect of alpha-MSH 11-13 (lysine-proline-valine) on fever in the rabbit." Peptides, 1984;5(4):815-7. PMID: 6333677.
- [Animal] Getting SJ, et al. "Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides." J Pharmacol Exp Ther, 2003;306(2):631-7. PMID: 12750433.
- [In Vitro] Elliott RJ, et al. "alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells." J Invest Dermatol, 2004;122(4):1010-9. PMID: 15102092.
- [Animal] Dalmasso G, et al. "PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation." Gastroenterology, 2008;134(1):166-78. PMID: 18061177.
- [Animal] Kannengiesser K, et al. "Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease." Inflamm Bowel Dis, 2008;14(3):324-31. PMID: 18092346.
- [In Vitro] Land SC. "Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists." Int J Physiol Pathophysiol Pharmacol, 2012;4(2):59-73. PMID: 22837805.
- [In Vitro] Pawar KR, et al. "Stability-indicating HPLC assay for lysine-proline-valine (KPV) in aqueous solutions and skin homogenates." Biomed Chromatogr, 2015;29(5):716-21. PMID: 25298219.
- [Animal] Viennois E, et al. "Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model." Cell Mol Gastroenterol Hepatol, 2016;2(3):340-357. PMID: 27458604.
- [Animal] Xiao B, et al. "Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis." Mol Ther, 2017;25(7):1628-1640. PMID: 28143741.
- [In Vitro] Pawar K, et al. "Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin." J Pharm Sci, 2017;106(7):1814-1820. PMID: 28343991.
- [Animal] Sun J, et al. "Self-Cross-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats." ACS Biomater Sci Eng, 2021;7(10):4859-4869. PMID: 34547895.
- [Animal] Zhao Y, et al. "A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon." Acta Biomater, 2022;143:233-252. PMID: 35245681.
- [In Vitro] Sung J, et al. "Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway." Tissue Cell, 2025;95:102837. PMID: 40073467.
- [Animal] An SH, et al. "KPV attenuates adipogenesis and lipid metabolism through modulation of ROS-mediated AKT/mTORC1/PPARγ signaling." Tissue Cell, 2026;104(Pt 1):103837. PMID: 42585803.
Sources & Citations
Every citation on this page is PubMed-indexed and has been checked against its record. Nine papers were added to our evidence set by hand after a title search, because the automatic search ranked unrelated uses of the abbreviation KPV first. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.