KPV

What it is

KPV (Lys-Pro-Val) is the C-terminal tripeptide (residues 11–13) of alpha-melanocyte-stimulating hormone (α-MSH), which is itself derived from proopiomelanocortin (POMC). KPV retains the anti-inflammatory capacity of the full α-MSH hormone but lacks the central pharmacophore required for binding to known melanocortin receptors (MC-Rs) and lacks pigmentary activity. At the molecular level, KPV inhibits NF-κB activation, suppresses MAP kinase inflammatory signaling pathways, and reduces pro-inflammatory cytokine secretion including IL-1β, TNF-α, IL-6, and IL-8. KPV is transported into intestinal epithelial cells and immune cells via the oligopeptide transporter PepT1 (also known as SLC15A1), which is normally expressed in the small intestine and induced in the colon during inflammatory bowel disease. In human keratinocytes, KPV signals via rapid intracellular calcium mobilization rather than cyclic AMP elevation. KPV has also demonstrated direct antimicrobial effects against Staphylococcus aureus and Candida albicans, potentially mediated by increases in cellular cAMP in target pathogens. One abstract notes that KPV, unlike full α-MSH, did not elicit inhibitory effects on basophil activation, which was attributed to KPV lacking the central pharmacophore of α-MSH. In the context of vascular calcification, KPV-RAPA nanoparticles were found to inhibit inflammatory responses. KPV has also been shown to inhibit ROS production and ROS-mediated caspase-1 activation, blocking pyroptosis in keratinocytes exposed to fine particulate matter.

Class: Anti-inflammatory tripeptide; C-terminal fragment of alpha-melanocyte-stimulating hormone (α-MSH)

What it's studied for

• Inflammatory bowel disease (ulcerative colitis, colitis) Animal studies only
  • Nanomolar concentrations of KPV inhibited NF-κB and MAP kinase pathways in intestinal epithelial cells and immune cells via PepT1 transporter; oral KPV reduced DSS- and TNBS-induced colitis in mice. PMID 51 Dalmasso et al., Gastroenterology (2008)
  • KPV-loaded nanoparticles encapsulated in polysaccharide (alginate-chitosan) hydrogel delivered KPV to inflamed colon in DSS-colitis mouse model; nanoparticle encapsulation allowed 12,000-fold lower KPV concentration with similar therapeutic efficacy compared to free KPV solution. PMID 49 Laroui et al., Gastroenterology (2010)
  • Hyaluronic acid-functionalized KPV nanoparticles (HA-KPV-NPs) encapsulated in chitosan/alginate hydrogel administered orally showed targeted delivery to colonic epithelial cells and macrophages, accelerating mucosal healing and alleviating inflammation in a mouse ulcerative colitis model, with stronger efficacy than no PMID 36 Xiao et al., Molecular Therapy (2017)
  • Self-immolative KPV prodrug conjugate (proKPV) achieved 3.8-fold greater colonic accumulation than free KPV in colitis mice, with enhanced efficacy at 20-fold lower dose; oral proKPV also accumulated in inflamed lungs and showed anti-inflammatory efficacy in acute lung injury mice. PMID 41533788 Cheng et al., Science Advances (2026)
  • Multicompartmental hydrogel microspheres with concentric oil layer protected KPV from acidic stomach conditions and maintained its anti-inflammatory and pro-healing activity on colonic epithelial cells. PMID 40030207 Jeong et al., ACS Applied Bio Materials (2025)
• Skin inflammation and wound healing (including PM-induced keratinocyte injury, oral mucositis, cutaneous wounds) Mixed
  • KPV at 50 µg/mL restored cell viability, reduced IL-1β secretion, inhibited ROS production, suppressed MAPK/NF-κB pathway, decreased apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3), and blocked caspase-1-mediated pyroptosis in PM10-treated human HaCaT keratinocytes; similar effects shown in a 3D skin model. PMID 40073467 Sung et al., Tissue & Cell (2025)
  • KPV@PPP_2%E hydrogel (tripeptide KPV dissolved in cold PLGA-PEG-PLGA/EGCG precursor solution) maintained anti-inflammatory activity and cell migration promotion; inhibited IL-1β and TNF-α, upregulated IL-10, improved food intake and body weight recovery in rats with chemotherapy-induced oral mucositis, and showed antib PMID 22 Shao et al., Biomaterials Science (2021)
  • Review proposing KPV and its derivative KdPT as promising candidates for cutaneous wound and skin ulcer treatment based on in silico, in vitro, ex vivo, and animal model data. PMID 30661264 Böhm & Luger, Experimental Dermatology (2019)
  • Review noting KPV-loaded hydrogels reduce inflammation, promote tissue regeneration, and combat MRSA infections in wound healing models. PMID 41209547 Adnan et al., International Journal of Medical Sciences (2025)
• Vitiligo (melanocyte-targeted delivery) Animal studies only
  • KPV-modified deformable liposomes (KPV-Lipos) carrying Nlrp3 shRNA were used to achieve melanocyte-specific knockdown of NLRP3, significantly alleviating vitiligo development in a melanoma-Treg-induced vitiligo mouse model. PMID 40935835 Zeng et al., Cell Death and Differentiation (2026)
• Vascular calcification Animal studies only
  • Carrier-free KPV-RAPA nanoparticles (KPV self-assembled with rapamycin) showed good stability and biosafety; significantly inhibited vascular calcification in mice in vivo and in vitro by inhibiting inflammatory responses and activating autophagy. PMID 12 Zhang et al., Advanced Healthcare Materials (2024)
• Anti-inflammatory and immunomodulatory effects (broad: contact hypersensitivity, arthritis, asthma, ocular inflammation) Animal studies only
  • Comprehensive review documenting KPV's anti-inflammatory effects validated in animal models of fever, contact dermatitis, vasculitis, fibrosis, ocular, gastrointestinal, brain, and allergic airway inflammation, and arthritis; KPV lacks pigmentary action of α-MSH. PMID 52 Brzoska et al., Endocrine Reviews (2008)
  • Review: most anti-inflammatory activities of α-MSH attributed to C-terminal tripeptide KPV; animal models support utility in contact dermatitis, vasculitis, asthma, IBD, rheumatoid arthritis, ocular and brain inflammation. PMID 53 Luger & Brzoska, Annals of the Rheumatic Diseases (2007)
  • KPV (α-MSH 11-13) reported to bind MC-1R and modulate antigen-presenting cell function; systemic and topical application of KPV inhibited sensitization and elicitation phase of contact hypersensitivity in mice and induced hapten-specific tolerance. PMID 56 Luger et al., Annals of the New York Academy of Sciences (2003)
  • Review: KPV retains almost all anti-inflammatory capacity of α-MSH but lacks pigmentary activity; exact signaling mechanism unknown but similarities with α-MSH anti-inflammatory signaling noted; KPV proposed for immune-mediated inflammatory skin and bowel diseases, allergic asthma, and arthritis. PMID 50 Brzoska et al., Advances in Experimental Medicine and Biology (2010)
• Antimicrobial activity (Staphylococcus aureus, Candida albicans) In vitro only
  • KPV (α-MSH 11-13) significantly inhibited S. aureus colony formation and reversed urokinase-enhanced colony formation; reduced C. albicans viability and germ tube formation; effects partly mediated via cellular cAMP increases; KPV enhanced, not reduced, human neutrophil killing of pathogens. PMID 57 Cutuli et al., Journal of Leukocyte Biology (2000)
  • KPV showed inhibitory influences against S. aureus and C. albicans in antimicrobial activity tests. PMID 59 Catania et al., Annals of the New York Academy of Sciences (2000)
• HIV-1 expression inhibition In vitro only
  • KPV reduced HIV-1 p24 antigen release in TNF-α-stimulated chronically infected U1 promonocytic cells and reduced HIV replication in acutely infected monocyte-derived macrophages; mechanism involved inhibition of NF-κB activation. PMID 60 Barcellini et al., Journal of Leukocyte Biology (2000)
• Chondroprotection / osteoarthritis (in vitro) In vitro only
  • α-MSH(KPV) (C-terminal peptide) was evaluated alongside MC1R and MC3R agonists on LPS-stimulated C-20/A4 chondrocytes for effects on cell viability, IL-6, IL-8, MMP-1, -3, -13, and HO-1 expression; results presented in context of comparing melanocortin peptide selectivity. PMID 26 Can et al., European Journal of Pharmacology (2020)
• Transdermal delivery / skin drug delivery In vitro only
  • KPV permeation across dermatomed human skin was below detectable levels by passive diffusion; microneedle (MN) treatment increased permeation to 4.4 µg/cm²/h; iontophoresis (ITP) and ITP+MN increased permeation 8- and 35-fold respectively vs. MN alone; skin retention elevated by all active methods vs. passive diffusion PMID 37 Pawar et al., Journal of Pharmaceutical Sciences (2017)
• Diagnostic probe target for ulcerative colitis imaging In vitro only
  • KPV conjugated to DCM chromophore (DCM-KPV) exploited PepT1 overexpression in chronic ulcerative colitis Caco-2 cells as a receptor-targeted fluorescent probe to discriminate chronic and acute colitis noninvasively in vitro. PMID 38 Zeng et al., ACS Applied Materials & Interfaces (2017)

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

Safety signals

• Chemical degradation of KPV under acidic, alkaline, and oxidative stress conditions, yielding lys-pro-diketopiperazine as a major degradation product; relevant to formulation stability and product integrity PMID 42
• No elevation in cyclic AMP detected in human keratinocytes (HaCaT and normal) in response to KPV at any tested concentration (10⁻¹⁵ to 10⁻⁷ M); signaling instead proceeds via intracellular calcium, suggesting receptor mechanism differs from full α-MSH PMID 55
• KPV, unlike full α-MSH, did not elicit effects on basophil activation in tested conditions, indicating it lacks certain immunomodulatory activities of the parent molecule PMID 48
• Peptides in the sports/bodybuilding context (including KPV) are associated with risks including cardiovascular strain, insulin resistance, dyslipidemia, and psychiatric instability; products are often mislabeled or contaminated due to unregulated supply chains PMID 3