KPV

What KPV is

KPV is the tripeptide Lys-Pro-Val, the last three residues of alpha-melanocyte-stimulating hormone (α-MSH), itself a 13-residue hormone cleaved from pro-opiomelanocortin. In the numbering of the parent hormone the tripeptide is α-MSH(11–13), the name under which much of the older literature files it. The free peptide, H-Lys-Pro-Val-OH, has a molecular formula of C16H30N4O4 and an average mass of 342.44 g/mol, which makes it, with GHK-Cu, one of the two smallest peptides in the catalogue.

The reason a three-residue fragment of a pigmentary hormone has a literature of its own is a paper from 1989. Melanie Hiltz and James Lipton, at the University of Texas Southwestern in Dallas, had been studying the antipyretic and anti-inflammatory effects of α-MSH and asked which part of the molecule carried them. They reported that the C-terminal tripeptide, synthesised on its own, inhibited inflammation in the mouse much as the full hormone did, while having none of its melanotropic (pigment-stimulating) activity [1]. That separation is the founding observation of the KPV literature, and most of what followed is an attempt to explain how a peptide that barely binds melanocortin receptors can have melanocortin-like effects.

Structurally there is little to say. The sequence has no cysteine, no non-natural residues and no lipid chain. The lysine side chain and the N-terminal amine give it a net positive charge at neutral pH. Research-grade KPV is supplied as a white lyophilised powder, as the acetate or trifluoroacetate salt depending on the purification route, and the certificate should say which. The reference identifiers for the free peptide are in the table.

How the literature describes its mechanism

The mechanism of KPV is an open question, because the obvious explanation does not fit. α-MSH acts through five G-protein-coupled melanocortin receptors (MC1R to MC5R), and its anti-inflammatory effects are usually attributed to MC1R on leukocytes and keratinocytes and MC3R on macrophages, with cyclic AMP as the second messenger. The receptor-binding region of α-MSH, however, is the central His-Phe-Arg-Trp motif at positions 6 to 9, not the C-terminal tripeptide, and KPV on its own has little or no measurable affinity for the cloned receptors. The reviews from Catania and Lipton, and later from the Münster group of Luger and Brzoska, say so plainly and present the tripeptide as a case where anti-inflammatory activity and receptor pharmacology have come apart [3, 4, 5, 6].

Three lines of evidence are usually cited. The first is structure–activity work: in 1991 Hiltz, Catania and Lipton synthesised analogues with the stereochemistry of individual residues altered and found that anti-inflammatory activity in the mouse survived substitutions that would normally abolish binding to a stereospecific receptor [2]. The second comes from macrophages: Mandrika, Muceniece and Wikberg in Uppsala reported in 2001 that melanocortin peptides inhibited lipopolysaccharide- and interferon-γ-induced NF-κB DNA binding and nitric oxide production in RAW 264.7 cells, with a pattern of effects that melanocortin-receptor signalling alone could not account for, hence the "dual mechanisms" of their title [7]. The third, and the most specific, is the intestinal work.

PepT1 uptake and NF-κB. In 2008 Guillaume Dalmasso and colleagues in Didier Merlin's laboratory at Emory University published, in Gastroenterology, a study whose premise was that a tripeptide is exactly the kind of molecule the intestinal oligopeptide transporter PepT1 is built to carry. Working with Caco2-BBE intestinal epithelial cells and Jurkat T cells, they reported that KPV at nanomolar concentrations reduced cytokine-induced activation of NF-κB and MAP kinase signalling and reduced pro-inflammatory cytokine secretion, and that these effects depended on PepT1: present in cells that express the transporter, absent in cells that do not, and conferred by expressing it. The authors proposed that KPV is carried into the cell by PepT1 and acts intracellularly on the NF-κB pathway, without engaging a surface receptor at all. The same paper reported that KPV given orally in drinking water reduced the incidence and severity of colitis in both the dextran sulphate sodium (DSS) and trinitrobenzene sulphonic acid (TNBS) models in mice, with lower expression of inflammatory cytokines in the colon [8].

The PepT1 hypothesis is attractive because it explains the receptor-independence, the activity of a fragment that lacks the receptor-binding motif, and the tissue in which the compound has been most studied, since PepT1 sits on the apical surface of enterocytes and is up-regulated in the inflamed colon. It is, though, one laboratory's model, concerning one cell type and one organ, and no published study has reconciled it with the earlier mouse ear and macrophage data, where PepT1 is not an obvious player. A fair summary is that KPV appears to act on the NF-κB pathway by a route that does not require melanocortin receptors, that in intestinal epithelium PepT1-mediated uptake is the best-supported explanation, and that the mechanism elsewhere is not settled [4, 6, 8].

For in-vitro work the published readouts are NF-κB translocation and DNA binding, phosphorylation of IκB and MAP kinases, IL-8 and TNF-α secretion from epithelial and immune cell lines, nitric oxide production from macrophages, and wound closure in epithelial monolayers. Concentrations run from low nanomolar to micromolar, and PepT1 expression by the chosen cell line is a variable worth controlling [8, 11].

The research record

KPV has no human clinical trial of any kind in the published literature, and no registered trial that we can find. That is the single most important fact about it. Everything below is from cells and animals.

The founding work, 1989–1991. Hiltz and Lipton's 1989 paper in the FASEB Journal is a short report. It showed that the tripeptide, given systemically to mice, reduced ear inflammation induced by the contact sensitiser picryl chloride, in a graded fashion, and did so without the pigmentary activity of the parent hormone [1]. The 1991 follow-up explored the stereochemistry of the three residues and found activity surprisingly tolerant of substitution [2]. Lipton and Catania's 1997 review in Immunology Today places this in the wider α-MSH story, including the hormone's antipyretic activity, its effects on cytokine production in human monocytes and its presence in human plasma and inflammatory exudates, and treats the tripeptide as a candidate "message sequence" for the anti-inflammatory effect [3].

The melanocortin reviews. The field's two major reviews, Catania and colleagues in Pharmacological Reviews in 2004 and Brzoska and colleagues in Endocrine Reviews in 2008, survey several hundred papers on α-MSH in models of fever, skin, joint, ocular, gut, brain and airway inflammation, and both present KPV and the related tripeptide KdPT as derivatives that keep the anti-inflammatory activity without the pigmentary one [4, 6]; Luger and Brzoska's 2007 piece in the Annals of the Rheumatic Diseases makes the same argument more briefly [5]. These are reviews by groups invested in the hypothesis and generous in their reading of the evidence, but they are the best maps of a scattered literature.

Colitis. The intestinal work is the strongest part of the record, with two independent groups publishing in the same year. Dalmasso and colleagues reported the PepT1 mechanism together with reduced DSS and TNBS colitis in mice given KPV orally [8]. Kannengiesser and colleagues in Münster reported in Inflammatory Bowel Diseases that KPV produced earlier recovery and greater regain of body weight in DSS colitis, reduced inflammatory infiltrates and colonic myeloperoxidase activity, and promoted recovery in the CD4+CD45RBhigh T-cell transfer model, a chronic, immunologically driven colitis. In mice with a non-functional MC1R (the recessive yellow MC1Re/e strain), KPV protected all treated animals from death during DSS colitis, which the authors offered as in-vivo evidence that the effect is at least partly MC1R-independent [9]. The two papers agree in outcome and on the receptor, though they differ on mechanism.

Nanoparticle delivery. The Emory group went on to use KPV as a model cargo for colon-targeted nanoparticles. Laroui and colleagues, in Gastroenterology in 2010, loaded KPV into polylactide nanoparticles, embedded them in an alginate–chitosan hydrogel designed to collapse at colonic pH, and gave the preparation orally to mice with DSS colitis. The headline result, cited in all the later work, was that encapsulated KPV reduced colitis to the same extent as free KPV in drinking water at a concentration roughly 12,000-fold lower [10]. Xiao and colleagues, from the same laboratory, extended this in Molecular Therapy in 2017 with PLGA nanoparticles functionalised with hyaluronic acid to target CD44 on colonic epithelial cells and macrophages. The targeted particles were taken up more efficiently in vitro, improved wound closure in Caco2-BBE monolayers, reduced lipopolysaccharide-induced TNF-α in RAW 264.7 macrophages, and in DSS colitis outperformed untargeted particles on body weight, colon length, histology and TNF-α expression, in groups of five mice [11]. These are formulation papers as much as pharmacology papers; their interest for a research programme is that KPV is a well-behaved, water-soluble cargo that survives encapsulation.

Brain injury. Schaible and colleagues in Mainz reported in PLoS ONE in 2013 that a single administration of the tripeptide after controlled cortical impact in mice reduced lesion volume and markers of inflammation and apoptosis in the injured hemisphere [12]. This is one study from one group and has not, as far as we can find, been independently replicated.

Antimicrobial activity. Cutuli, Cristiani, Lipton and Catania reported in the Journal of Leukocyte Biology in 2000 that α-MSH and its C-terminal fragments, including the tripeptide, reduced the viability of Staphylococcus aureus and Candida albicans in vitro and inhibited germ-tube formation in Candida, with the anti-Candida effect associated with a rise in fungal cyclic AMP, implying a mechanism distinct from the membrane disruption of classical antimicrobial peptides [13]. Singh and Mukhopadhyay's 2014 review collects the subsequent work, mainly on S. aureus, and notes that the C-terminal fragments retain activity comparable to the full hormone [14]. The antimicrobial literature is small and in vitro; the observation is reproducible across groups, but reported potencies vary widely with assay conditions.

What is missing. There is no pharmacokinetic study of KPV in any species that we can find in the peer-reviewed literature: no half-life, no bioavailability, no metabolism data. A tripeptide would be expected to be cleaved rapidly by plasma and tissue peptidases, and the nanoparticle literature exists partly because of that expectation, but it has not been measured and published. There is no formal toxicology and no human exposure data of any kind. No binding study establishes a target, and the PepT1 model has not been tested outside the gut. The colitis findings are replicated across two groups; for every other model the record is a single laboratory.

Taking the record as a whole. KPV is a small, well-defined fragment with a consistent anti-inflammatory signal in rodent models from several laboratories over three decades, a plausible and partly tested receptor-independent mechanism, an in-vitro antimicrobial literature, and no human data at all. That is an adequate basis for in-vitro research into NF-κB signalling, epithelial biology and peptide transport. It is not a basis for therapeutic claims of any kind, and this page makes none.

Regulatory status in the United Kingdom

KPV is not licensed as a medicine in the UK or anywhere else. It has no marketing authorisation, no monograph in any pharmacopoeia and no approved therapeutic use; nor is the parent hormone α-MSH licensed. BuyUK Peptides supplies KPV as a research chemical for in-vitro laboratory use under the Terms of Sale. It is not for human or veterinary administration. Purchasers must be 18 or over and are responsible for ensuring their use of the material complies with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail.

KPV is not named on the World Anti-Doping Agency's 2026 Prohibited List, and neither is α-MSH or any other melanocortin peptide; we checked the published list, in force from 1 January 2026 [15]. It does not follow that the compound is permitted in sport. Category S0, non-approved substances, covers any pharmacological substance not addressed elsewhere on the List and with no current approval by any governmental regulatory health authority for human therapeutic use, and is prohibited at all times. KPV meets that description, and BPC-157 is now the List's worked example of an S0 substance. Any researcher whose institution is subject to anti-doping rules should treat KPV as prohibited under S0.

Handling, storage and stability

KPV is supplied lyophilised in a glass vial with a rubber stopper and an aluminium flip-off crimp. As a three-residue, unlipidated, cysteine-free peptide it is about as straightforward to handle as a peptide can be. The one feature that deserves attention is the lysine, whose side-chain amine will react with reducing sugars if the compound is stored in buffers that contain them.

Sealed vial. Store at 2–8 °C for routine use and at −20 °C or below for storage beyond a few months. Protect from light as a precaution; the sequence contains no tryptophan, tyrosine or methionine. Avoid repeated freeze–thaw cycles. Allow a refrigerated vial to reach room temperature before opening so that moisture does not condense onto the hygroscopic cake.

Reconstitution. For most in-vitro work the compound is reconstituted in sterile water, phosphate-buffered saline or the assay medium. A charged tripeptide of this size dissolves instantly; add the solvent down the side of the vial and swirl. There is no need for sonication, warming or organic co-solvent. The reconstitution calculator gives the volume to add for a target concentration. Because the molecular weight is low, a 10 mg vial gives a stock in the tens of millimolar range, so it is worth planning the dilution series before opening the vial.

Reconstituted solution. Keep at 2–8 °C. There are no published chemical stability data for KPV in aqueous solution. In clean buffer a tripeptide with no labile residues should be stable for weeks at 2–8 °C; the conservative practice is to use a solution within 28 days or to aliquot and freeze at −20 °C. In serum-containing medium the compound should be assumed to be a peptidase substrate, so a user replicating the Emory cell work should treat the timing of exposure as a variable [8].

Solubility. KPV acetate is freely soluble in water and aqueous buffers across the physiological pH range. It does not aggregate, foam or adsorb appreciably to plastics, and passes a 0.22 µm filter without loss. At high concentrations the counter-ion affects the pH of an unbuffered solution, so a concentrated stock in water should have its pH checked before use.

What a sound certificate for KPV looks like

Every batch we release carries an independent certificate of analysis, and the figures from it are transcribed on the product page and in the certificate register. For a tripeptide the analytical picture is simpler than for a long peptide, and expectations are correspondingly higher.

Purity by RP-HPLC. Reversed-phase HPLC on a C18 column with UV detection at 214 nm reports purity as the area of the main peak as a percentage of all integrated peaks. KPV has no aromatic residue and negligible absorbance at 254 or 280 nm, so a certificate reporting purity at those wavelengths should be questioned. A tripeptide is also very polar and elutes early on C18, so the chromatogram should show the main peak resolved from the injection front. A good batch shows purity of 98% or above; 99% and above is routine for a sequence this short. The plausible impurities are the dipeptides Lys-Pro and Pro-Val, free amino acids, and the diketopiperazine formed by cyclisation of the N-terminal Lys-Pro, a well-known side reaction for sequences with proline in the second position.

Identity by LC-MS. Electrospray mass spectrometry confirms that the main peak has the expected mass. The average molecular weight of free KPV is 342.44 Da and the monoisotopic mass 342.23 Da; the compound appears almost exclusively as the singly charged [M+H]+ ion at m/z 343.2, with a doubly charged ion at m/z 172.1 sometimes visible. The observed mass should agree with theory to within 0.2 Da. A peak at m/z 325.2, 18 Da lower, would indicate the diketopiperazine and should prompt a question.

Net peptide content. For a short, basic peptide the counter-ion fraction is large. A molecule with two basic sites can carry two acetate or trifluoroacetate ions, and the trifluoroacetate salt of KPV may contain as little as 60% peptide by mass once bound water is included. This matters more for KPV than for most compounds in the catalogue: a stock prepared by gross weight will be substantially less concentrated than the nominal figure unless net peptide content is taken into account. A certificate that reports it, or at least names the counter-ion, is materially more useful than one that reports purity alone.

Endotoxin. Where the batch has been tested, a limulus amoebocyte lysate (LAL) result is reported in endotoxin units per milligram. This matters for KPV because the published in-vitro work concerns NF-κB signalling and cytokine release in epithelial and macrophage lines, where endotoxin contamination of the test compound would produce the opposite of the expected effect.

Our guide to reading a certificate of analysis goes through a complete report line by line.

Related compounds

KPV's nearest relative in the catalogue is Melanotan II, a cyclic synthetic analogue of α-MSH built around the His-Phe-Arg-Trp receptor-binding motif that KPV lacks; the two together illustrate the division of the parent hormone into a receptor-binding region and a putative anti-inflammatory one, and MT-2 is the obvious comparator for any experiment testing whether an effect of KPV is melanocortin-receptor-dependent. BPC-157 shares with KPV a rodent colitis literature, though it is five times the length, has a different and equally undefined mechanism, and is now the WADA List's named example of an S0 substance. GHK-Cu is the other tripeptide we supply and the one whose handling most resembles KPV at the bench; its biology, through copper delivery and gene expression in skin, is unrelated.

Frequently asked questions

Is KPV a hormone? No. It is a fragment of one. The three C-terminal residues of α-MSH on their own do not bind melanocortin receptors to any useful extent and do not stimulate pigmentation [1, 4].

How can it have melanocortin-like effects without binding melanocortin receptors? That is the central question of the literature. The best-supported answer, in intestinal cells, is uptake through PepT1 followed by inhibition of NF-κB signalling inside the cell [8]; the mechanism elsewhere has not been established.

Are there any human trials? None, published or registered, that we can find. The entire record is in cell lines and rodents.

Is it on the WADA list? It is not named [15], but it falls within the S0 category of non-approved substances, which is prohibited at all times.

What is the difference between KPV and KdPT? KdPT (Lys-D-Pro-Thr) is a different tripeptide, derived from residues 193–195 of interleukin-1β, which the Münster group studies alongside KPV [5, 6]. They are not interchangeable; the material sold here is KPV only.

How long does a sealed vial last? A short, unlipidated, cysteine-free peptide of this kind is stable for years at −20 °C and for many months at 2–8 °C. The batch certificate reports the test date; the storage guidance on this page applies from receipt.

References

1. Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide α-MSH. FASEB Journal. 1989;3(11):2282–2284. doi:10.1096/fasebj.3.11.2550304. PMID 2550304.
2. Hiltz ME, Catania A, Lipton JM. Anti-inflammatory activity of α-MSH(11–13) analogs: influences of alteration in stereochemistry. Peptides. 1991;12(4):767–771. doi:10.1016/0196-9781(91)90131-8.
3. Lipton JM, Catania A. Anti-inflammatory actions of the neuroimmunomodulator α-MSH. Immunology Today. 1997;18(3):140–145. doi:10.1016/S0167-5699(97)01009-8.
4. Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacological Reviews. 2004;56(1):1–29. doi:10.1124/pr.56.1.1.
5. Luger TA, Brzoska T. α-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Annals of the Rheumatic Diseases. 2007;66(Suppl 3):iii52–iii55. doi:10.1136/ard.2007.079780. PMID 17934097.
6. Brzoska T, Luger TA, Maaser C, Abels C, Böhm M. α-Melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocrine Reviews. 2008;29(5):581–602. doi:10.1210/er.2007-0027. PMID 18612139.
7. Mandrika I, Muceniece R, Wikberg JES. Effects of melanocortin peptides on lipopolysaccharide/interferon-γ-induced NF-κB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. Biochemical Pharmacology. 2001;61(5):613–621. doi:10.1016/S0006-2952(00)00583-9.
8. Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166–178. doi:10.1053/j.gastro.2007.10.026. PMID 18061177.
9. Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. 2008;14(3):324–331. doi:10.1002/ibd.20334. PMID 18092346.
10. Laroui H, Dalmasso G, Nguyen HTT, Yan Y, Sitaraman SV, Merlin D. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010;138(3):843–853.e2. doi:10.1053/j.gastro.2009.11.003. PMID 19909746.
11. Xiao B, Xu Z, Viennois E, et al. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Molecular Therapy. 2017;25(7):1628–1640. doi:10.1016/j.ymthe.2016.11.020. PMID 28143741.
12. Schaible EV, Steinsträßer A, Jahn-Eimermacher A, et al. Single administration of tripeptide α-MSH(11–13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice. PLoS ONE. 2013;8(8):e71056. doi:10.1371/journal.pone.0071056.
13. Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of α-MSH peptides. Journal of Leukocyte Biology. 2000;67(2):233–239. doi:10.1002/jlb.67.2.233. PMID 10670585.
14. Singh M, Mukhopadhyay K. Alpha-melanocyte stimulating hormone: an emerging anti-inflammatory antimicrobial peptide. BioMed Research International. 2014;2014:874610. doi:10.1155/2014/874610. PMID 25140322.
15. World Anti-Doping Agency. The Prohibited List 2026. Effective 1 January 2026. wada-ama.org/en/prohibited-list.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.