KPV
Lys-Pro-Val (alpha-MSH C-terminal tripeptide, residues 11-13)
C-terminal tripeptide fragment (residues 11-13) of alpha-melanocyte stimulating hormone (alpha-MSH) with potent anti-inflammatory activity mediated by PepT1 transporter uptake and NF-kB inhibition, studied exclusively in animal models and cell culture with no published human clinical trials (PMID 18612139, PMC 2431115).
Last updated: 2026-03-10
Safety Summary
A reliable clinical adverse-effect profile has not been established. No formal human safety studies have been published. The FDA noted in 2023 that it 'lacks important information regarding any safety issues raised by KPV, including whether it would cause harm if administered to humans' (FDA.gov). The source pack contains no human trial or approved-label safety dataset. Animal studies describe KPV as a 'naturally derived tripeptide without any notable side effects'. Community reports generally describe KPV as well-tolerated, though some users report paradoxical GI upset, particularly at higher doses or early in treatment. Unlike full-length alpha-MSH, KPV does not cause skin darkening or hormonal disruption because it lacks melanogenic activity (PMID 18612139). The side effects listed above are derived from practitioner reports and community anecdotes, not formal clinical data. The absence of long-term human safety data remains a significant limitation.
Known Side Effects
uncommon
uncommon
rare
rare
Who Should NOT Use This
FDA lists KPV in 503A Category 2 and states that it has not identified human exposure data for any route and lacks sufficient information to know whether the drug would cause harm in humans.
No reproductive safety data available. Practitioners contraindicate use in pregnant/breastfeeding women as standard precaution.
Caution advised due to theoretical concerns about immunomodulation in cancer context. One study showed KPV therapeutic benefit in colitis-associated cancer model but also noted PepT1 role in promoting colitis-associated cancer (PMID 27458604). Practitioners recommend cancer screening before use.
Anti-inflammatory and immunomodulatory effects may interact with immunosuppressive medications. No published interaction studies. Theoretical concern based on mechanism.
Talk to Your Doctor
Before considering KPV, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-12]
Evidence Assessment
Tier 5: Animal/in vitro only. All published efficacy data comes from cell culture studies and mouse models of colitis (DSS, TNBS). No human clinical trials have been published. The FDA explicitly stated in September 2023 that it has 'not identified any human exposure data on drug products containing KPV administered via any route of administration' (FDA.gov). The source pack contains no ClinicalTrials.gov studies for KPV. However, preclinical evidence is robust, with multiple independent groups demonstrating anti-inflammatory efficacy in animal models (PMC 2431115, PMID 19909746, PMC 5498804, PMID 41533788) and well-characterized molecular mechanism (PMC 3403564).
1New insights into the functions of alpha-MSH and related peptides in the immune system.PMID 12851308
Luger TA et al. - Annals of the New York Academy of Sciences (2003) - review + experimental - Mouse models of contact hypersensitivity + cell cultures
Reported that KPV was able to bind MC-1R and modulate APC function. Systemic and topical alpha-MSH/KPV inhibited sensitization and elicitation phases of contact hypersensitivity (CHS). Induced hapten-specific tolerance via CTLA4+ and IL-10-producing T lymphocytes. Alpha-MSH modulated IgE production and reduced allergen-specific IgE, eosinophil influx, and IL-4 in allergic airway model. IL-10 knockout mice resistant to treatment, confirming IL-10 mediation. Note: MC1R binding claim was later contradicted by more specific binding studies cited in Dalmasso 2008 (PMC 2431115).
Limitations: Mouse models. Mixed alpha-MSH and KPV data -- not all findings are KPV-specific. MC1R binding claim contradicted by later studies.
2Alpha-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.PMID 18612139
Brzoska T et al. - Endocrine Reviews (2008) - review - N/A (comprehensive review)
Comprehensive review establishing that KPV retains the anti-inflammatory effects of alpha-MSH without its pigmentary action. KPV effects validated in animal models of contact dermatitis, vasculitis, fibrosis, GI inflammation, brain inflammation, airway inflammation, and arthritis. KPV and KdPT identified as suitable candidates for future treatment of immune-mediated inflammatory skin/bowel disease, fibrosis, lung disease, ocular inflammation, and arthritis.
Limitations: Review paper synthesizing existing literature. No new experimental data presented.
3PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation.
Dalmasso G et al. - Gastroenterology (2008) - in vitro + animal study - Multiple groups of mice (DSS and TNBS models) + cell culture (Caco2-BBE, THP-1 monocytes)
Landmark study demonstrating: (1) KPV anti-inflammatory effect is PepT1-mediated, not melanocortin receptor-mediated; (2) KPV inhibits IkB-alpha degradation and NF-kB activation in Caco2-BBE cells; (3) KPV significantly reduced weight loss, MPO activity, and histological damage in DSS-induced colitis; (4) KPV attenuated colitis in TNBS model; (5) alpha-MSH did not replicate KPV effects in intestinal cells, confirming non-MCR mechanism; (6) PepT1 overexpression enhanced KPV anti-inflammatory response. KPV does not bind to MC1,3,5R and does not compete with alpha-MSH.
Limitations: Mouse models only. No human subjects. DSS and TNBS models may not fully recapitulate human IBD pathophysiology.
4Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model.PMID 19909746
Laroui H et al. - Gastroenterology (2010) - in vitro + animal study - DSS colitis mouse model + Caco2-BBE cells
KPV-loaded nanoparticles (400nm) encapsulated in alginate-chitosan hydrogel successfully targeted colon delivery. NP-KPV reduced inflammatory responses dose-dependently in vitro and protected against colitis in vivo. Critical finding: nanoparticle delivery achieved equivalent efficacy at a 12,000-fold lower KPV concentration compared to free KPV in solution.
Limitations: Mouse model only. Nanoparticle formulation complexity may limit clinical translation. Single colitis model (DSS).
5Inhibition 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.
Land SC - International Journal of Physiology, Pathophysiology and Pharmacology (2012) - in vitro - Human bronchial epithelial cell cultures (16HBE14o-)
Elucidated KPV mechanism: KPV inhibits p65RelA nuclear translocation by competitive interaction with importin-alpha3 (Imp-alpha3) arm domains 7-8. This mechanism is independent of melanocortin receptors. Demonstrated that KPV suppresses NFkB signaling in airway epithelium, suggesting potential for lung disease. Also showed gamma-MSH acts via MC3R activation -- a separate pathway.
Limitations: Single cell line (human bronchial epithelial). In vitro only. Pepsite computational analysis for binding site prediction, not crystallographic confirmation.
6Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model.PMID 27458604
Viennois E et al. - Cellular and Molecular Gastroenterology and Hepatology (2016) - animal study - Murine colitis-associated cancer model
Demonstrated dual role of PepT1: it promotes colitis-associated cancer progression, yet PepT1-mediated delivery of KPV provides therapeutic benefit in the same model. KPV treatment showed anti-inflammatory effects that may be at least partially independent of MC1R signaling.
Limitations: Animal model only. Complex interaction between PepT1 cancer-promoting and KPV therapeutic roles requires further study.
7Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles.
Viennois E et al. - Molecular Therapy (2017) - in vitro + animal study - DSS colitis mouse model + Caco2-BBE cells + macrophage cultures
Hyaluronic acid-functionalized KPV nanoparticles (HA-KPV-NPs) showed enhanced cellular uptake by colonic epithelial cells and macrophages compared to non-functionalized KPV-NPs. HA-KPV-NPs accelerated mucosal healing and alleviated inflammation with much higher efficiency. Treated mice showed parameters (body weight, MPO, colon length, spleen weight, histology) very similar to healthy controls. Demonstrated wound healing promotion via ECIS technology.
Limitations: Mouse model only. Complex nanoparticle formulation. No human studies.
8Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers.PMID 41533788
Cheng J et al. - Science Advances (2026) - in vitro + animal study - DSS colitis mice + acute lung injury mice + multiple peptides tested (KPV, Ac-QAW, IRW)
Self-immolative peptide prodrug conjugate (SIPPC) platform for inflammation-targeted oral delivery. KPV-based conjugate (proKPV) achieved 3.8-fold greater colonic accumulation than free KPV. Enhanced efficacy at 20-fold lower dose than free KPV. Beyond colitis, oral proKPV substantially accumulated in inflamed lungs and showed potent anti-inflammatory efficacy in acute lung injury model. Platform validated with multiple peptides.
Limitations: Mouse models only. Novel delivery platform not yet tested in humans. Prodrug approach adds complexity.
9The melanocortin system in control of inflammation.PMID 20852827
Catania A et al. - TheScientificWorldJournal (2010) - review - N/A (review)
Review covering melanocortin peptides as anti-inflammatory and immunomodulatory agents. Documented anticytokine action and inhibitory effects on inflammatory cell migration. Effectiveness in acute, chronic, and systemic inflammatory disorders in preclinical studies. Melanocortins identified as promising compounds for neuroprotection.
Limitations: Review paper. Does not provide KPV-specific new data.
10Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes.PMID 32004526
Can VC et al. - European Journal of Pharmacology (2020) - in vitro - Chondrocyte cell cultures
KPV demonstrated anti-inflammatory and chondroprotective effects on LPS-activated chondrocytes through melanocortin signaling pathways.
Limitations: In vitro study only. Chondrocyte model. Study primarily focused on MC1R and MC3R agonists, not KPV specifically.
11[Changes in aldosterone binding activity of kidney cytosol after stress in rats and the regulation].PMID 11833422
Not specified (Chinese language paper) - Not specified (2001) - animal study - Rat scald injury model
Injection of alpha-MSH and KPV peptide (Ac-D-Lys-L-Pro-D-Val) prevented the decrease in aldosterone binding activity in kidney cytosol of rats with heavy-degree scald injury. Anti-TNF-alpha and anti-IL-1beta antibodies produced similar protective effects, suggesting KPV acts through anti-inflammatory pathways in this model.
Limitations: Animal study. Chinese language paper with English abstract only. Small study. KPV stereoisomer (D-form) used. Indirect measure of anti-inflammatory effect.
12Inflammation and neuropeptides: the connection in diabetic wound healing.PMID 19138453
Pradhan L et al. - Expert Reviews in Molecular Medicine (2009) - review - N/A (review)
Review of the bidirectional connection between the nervous and immune systems in wound repair. Covers neuropeptides including alpha-MSH family as mediators of wound healing. Provides context for KPV's potential role in wound healing through neuroimmune axis modulation.
Limitations: Review paper. Does not provide KPV-specific experimental data. Focused on diabetic wound healing context.