Compound reference
KPV
Also known as Lys-Pro-Val
KPV (Lys-Pro-Val) is the C-terminal anti-inflammatory fragment of alpha-MSH, with deep, reproducible, multi-lab preclinical evidence in colitis and wound models — and a genuinely elegant gut-uptake mechanism. But there is no completed human trial of KPV itself; the one controlled study tests a derivative.
- CAS
- 67727-97-3
- Formula
- C₁₆H₃₀N₄O₄ (free tripeptide)
- Molar mass
- ≈342.4 g/mol
- Sequence
- Lys-Pro-Val — the C-terminal tripeptide of alpha-MSH (residues 11-13)
Research peptide; not FDA-approved as a drug.
Mode of action
KPV is the tripeptide lysine-proline-valine — the C-terminal three residues of α-melanocyte-stimulating hormone (α-MSH 11-13). Its design logic is subtractive: α-MSH is a potent anti-inflammatory hormone, but it also drives pigmentation through the His-Phe-Arg-Trp "pharmacophore" that binds melanocortin receptors. KPV keeps the anti-inflammatory tail and discards that pharmacophore, so it retains the immune-calming activity without the tanning or hormonal melanocortin signaling.
Two mechanistic features stand out. First, its anti-inflammatory action is largely receptor-independent: KPV does not reliably raise intracellular cAMP and does not require MC1R or MC3/4R to work (in keratinocytes it mobilizes calcium rather than cAMP, and in peritonitis its effect survives melanocortin-receptor blockade). What it does instead is suppress NF-κB activation — stabilizing IκBα and blocking the nuclear translocation of p65/RelA — which lowers production of IL-1β, IL-6, TNF-α, IFN-γ and IL-8. Second, and more distinctive, is how it gets into cells in the gut: KPV is a substrate for PepT1, the intestinal di/tripeptide transporter, which carries it into both epithelial and immune cells at nanomolar concentrations. Because PepT1 is upregulated in inflamed intestine, this gives KPV a measure of built-in targeting and explains why it is active orally at very low doses. KPV also has direct antimicrobial activity against organisms such as Staphylococcus aureus and Candida albicans.
Main intended effect
Anti-inflammation — particularly of the intestinal mucosa — together with antimicrobial activity and support of wound and mucosal repair.
Areas of interest
The lead area by a wide margin is inflammatory bowel disease, especially ulcerative colitis, where the PepT1-targeting and oral-nanoparticle-delivery work form a substantial subfield. Secondary interests include wound healing (corneal, diabetic, and chemotherapy-induced oral mucositis), inflammatory skin conditions, and more exploratory uses such as neuroprotection after traumatic brain injury and hepatic lipid regulation. In the consumer market KPV is sold as a gut-health and anti-inflammatory research peptide.
Evidence for intended effects
Unlike the single-lab story behind many research peptides, KPV's preclinical base is deep and reproduced across independent groups. In DSS- and TNBS-induced colitis, oral KPV consistently reduces inflammation, acting at nanomolar potency through PepT1; its anti-tumor and anti-inflammatory effects in the gut are abolished in PepT1-knockout animals, confirming the transporter's central role. Nanoparticle and hydrogel delivery systems sharpen the effect further — one approach lowered the effective dose several thousand-fold while improving mucosal targeting. Beyond the gut, KPV accelerates corneal and diabetic wound healing, eases oral mucositis, and reduces lesion size and apoptosis after experimental TBI.
The human evidence, however, is the missing piece. There is no completed randomized trial of KPV itself. The closest controlled human data come from a phase IIa trial in mild-to-moderate ulcerative colitis — but that study tested K(D)PT (Lys-D-Pro-Thr), a protease-stabilized derivative of the same α-MSH tail, not KPV. K(D)PT was well tolerated with placebo-like safety and showed modest efficacy signals. A KPV dimer, (CKPV)₂, has also entered clinical investigation. So the family has a foothold in humans; the specific molecule sold as "KPV" does not.
| Strand | What exists | Tier |
|---|---|---|
| Gut / colitis (preclinical) | DSS/TNBS models, PepT1-dependence, delivery systems | Strong, multi-lab preclinical |
| Wound / mucosal healing | Corneal, diabetic, oral-mucositis models | Preclinical |
| Mechanism | PepT1 uptake + NF-κB suppression; receptor-independent | Well characterized |
| Human — KPV itself | None | No trials |
| Human — family | K(D)PT phase IIa in UC (a derivative) | Limited human (derivative) |
Studied amounts (literature dosing context)
Reported amounts are preclinical. Colitis models used oral KPV around 100 µM in drinking water; corneal studies used 1, 5, or 10 mg/mL drops; the TBI study used a single 1 mg/kg intraperitoneal dose; and nanoparticle formulations cut the effective dose by roughly four orders of magnitude. The one human trial in this family used oral K(D)PT (the derivative) at 20, 50, or 100 mg twice daily. There is no established human dose for KPV, and this page does not provide dosing guidance.
Safety and regulatory status
KPV is generally well tolerated in preclinical models, and its derivative K(D)PT had a placebo-like safety profile in its phase IIa ulcerative-colitis trial — encouraging, but not a substitute for human safety data on KPV itself, which does not exist. Reviews also note practical limits that constrain translation: rapid proteolytic degradation in vivo and poor penetration across skin, which is much of the rationale for the elaborate delivery systems in the colitis literature.
KPV is not an FDA-approved drug; it is a research peptide, typically sold as a lyophilized powder for reconstitution. As with other gray-market peptides, products labeled "KPV" are unregulated and show high rates of identity and purity failure, so the contents of any given vial are not assured.
Sources
Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo
Comprehensive review by Brzoska, Luger, Maaser, Abels, and Böhm (Endocr Rev, 2008) examining the biochemistry and therapeutic potential of alpha-MSH and related tripeptides — principally KPV and KdPT — in immune-mediated inflammatory disease. The authors describe how alpha-MSH acts through melanocortin receptors to activate descending neurogenic anti-inflammatory pathways and to suppress NF-kappaB, adhesion molecule expression, chemokine receptor signalling, and pro-inflammatory cytokine production in peripheral immune cells. KPV retains these anti-inflammatory properties while lacking alpha-MSH's pigmentary action, providing a practical therapeutic advantage. Evidence is drawn from dermatitis, vasculitis, fibrosis, gastrointestinal inflammation, arthritis, and organ-injury models. The authors propose that improved physicochemical properties and lower synthesis costs position tripeptides as viable drug candidates for inflammatory skin, bowel, pulmonary, and arthritic conditions.
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation
Mechanistic study (Dalmasso and colleagues) combining intestinal epithelial cell lines (Caco2-BBE, HT29-Cl.19A), human T cells (Jurkat), and both DSS- and TNBS-induced mouse colitis models to characterize how KPV (Lys-Pro-Val) enters cells and suppresses inflammation. KPV was taken up into intestinal epithelial and immune cells via the PepT1 di/tripeptide transporter, and at nanomolar concentrations (as low as 10 nM) inhibited NF-κB and MAP kinase activation and significantly reduced secretion of IL-6, IL-12, IFN-γ, IL-1β, and TNF-α (p < 0.05). Oral KPV administration via drinking water at 100 µM decreased pro-inflammatory cytokine expression and reduced disease severity in both mouse colitis models. The PepT1-dependent transport distinguishes KPV's uptake route from larger MSH peptides and explains its bioavailability at nanomolar potency. These findings are from cell lines and mouse colitis models; therapeutic efficacy in human inflammatory bowel disease has not been established in controlled trials.
Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides
Mouse peritonitis study (Getting and colleagues) using a crystal-induced model to dissect the anti-inflammatory contributions of alpha-MSH, its core melanocortin tetrapeptide, the synthetic MC3/4 agonist MTII, the selective MC1R agonist MS05, and the C-terminal tripeptide KPV. KPV, alpha-MSH, and MTII all significantly reduced polymorphonuclear leukocyte accumulation in the peritoneal cavity, whereas MC1R-selective MS05 had no effect. Critically, the anti-migratory effect of KPV was not blocked by an MC3/4-R antagonist, and KPV failed to elevate cAMP in vitro, distinguishing its mechanism from canonical melanocortin-receptor signaling. The authors conclude that KPV is more likely to mediate its anti-inflammatory effects through inhibition of IL-1beta-driven functions than through melanocortin receptors. These are mouse peritonitis findings; efficacy in other inflammatory conditions or in humans requires separate investigation.
Alpha-melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells
In vitro signaling study in human keratinocyte cells comparing the intracellular second-messenger responses to alpha-melanocyte-stimulating hormone, its C-terminal tripeptide KPV (MSH 11-13), and adrenocorticotropic hormone. Unlike alpha-MSH, KPV did not elevate intracellular cAMP, indicating it does not signal through the canonical MC1R-adenylyl cyclase axis in these cells. Instead, KPV was associated with rapid mobilization of intracellular calcium, pointing to a distinct, non-cAMP second-messenger route. This mechanistic dissociation between receptor-coupled cAMP signaling and calcium-dependent pathways may explain why KPV retains anti-inflammatory activity in contexts where classical melanocortin receptors are absent or pharmacologically blocked. Findings are from an in vitro keratinocyte model; signaling pathway identity and relevance in intact skin or in vivo inflammatory conditions requires further characterization.
Terminal signal: anti-inflammatory effects of alpha-melanocyte-stimulating hormone related peptides beyond the pharmacophore
Review chapter published in Advances in Experimental Medicine and Biology (2010) examining how the C-terminal sequence of alpha-MSH — the tripeptide KPV and related analogues — exerts anti-inflammatory activity through mechanisms that extend beyond activation of the classical melanocortin receptors. The authors discuss evidence that these terminal fragments can modulate innate and adaptive immune responses at the cellular level, including effects on cytokine production and signalling pathways not fully explained by canonical MC-receptor engagement. The chapter situates KPV within the broader concept that the pharmacophore (His-Phe-Arg-Trp) responsible for melanocortin receptor binding is not strictly required for anti-inflammatory efficacy. The work underscores the potential for developing receptor-independent or alternatively-targeted therapeutic derivatives with improved selectivity profiles.
Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis
Preclinical study evaluating oral delivery of the tripeptide KPV encapsulated in ~272 nm hyaluronic-acid-functionalized polymeric nanoparticles embedded in a chitosan/alginate hydrogel, tested in DSS-induced colitis mice (daily gavage for 6 days) and in Colon-26 epithelial and RAW 264.7 macrophage cell lines in vitro. Hyaluronic-acid functionalization significantly increased nanoparticle internalization by both epithelial cells and macrophages (p < 0.05–0.01) compared with non-functionalized particles. In vivo, HA-KPV nanoparticles reduced colonic myeloperoxidase activity, spleen weight, and TNF-α mRNA expression and preserved colon length relative to untreated colitic controls. The dual mechanism — receptor-mediated mucosal targeting via hyaluronic acid combined with KPV's intrinsic anti-inflammatory activity — produced both anti-inflammatory and mucosal-healing effects. All results are from a mouse DSS-colitis model; human inflammatory bowel disease translation requires clinical evaluation.
Single administration of tripeptide alpha-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice
Controlled cortical impact study in male C57Bl/6N mice in which a single intraperitoneal dose of KPV [alpha-MSH(11-13), 1 mg/kg] was administered 30 minutes after standardized traumatic brain injury (n = 10 per group). KPV reduced secondary lesion volume by approximately 24% versus vehicle controls (21.0 ± 3.4 mm³ vs. 27.7 ± 4.8 mm³; p = 0.016) and decreased cleaved caspase-3/NeuN-positive apoptotic neurons by approximately 52% (26 ± 10 vs. 55 ± 19 cells/ROI; p = 0.002). Activated (amoeboid) microglia were also significantly reduced in the ipsilateral hemisphere (p = 0.002–0.033). A pre-injury time-course showed MC1R mRNA peaked approximately 3-fold at 12 hours post-injury. The authors propose dual anti-inflammatory and anti-apoptotic protection, potentially involving MC4R-mediated ERK1/2 and Bax/Bcl-2 modulation, rather than cytokine suppression alone. All findings are from a single-dose, single-species mouse model assessed at 24 hours; longer-term outcomes and human TBI applicability require further investigation.
Are melanocortin peptides future therapeutics for cutaneous wound healing?
Review published in Experimental Dermatology (2019) evaluating whether truncated melanocortin peptides — particularly the C-terminal tripeptide KPV — represent viable future therapeutics for cutaneous wound healing. The authors discuss preclinical evidence that KPV and related alpha-MSH fragments modulate the inflammatory phase of wound repair through melanocortin receptor-dependent and receptor-independent pathways, suppressing pro-inflammatory cytokine release without inducing the skin pigmentation associated with full-length alpha-MSH. The review addresses wound-healing stages (haemostasis, inflammation, proliferation, remodelling) and maps reported melanocortin peptide actions onto each phase. The authors conclude that the anti-inflammatory selectivity of truncated peptides is pharmacologically promising, but note that translation is constrained by limited in vivo evidence and the absence of controlled clinical wound-healing trials at the time of publication.
Exploring the role of tripeptides in wound healing and skin regeneration: a comprehensive review
Comprehensive review by Adnan, Maarof, Fauzi, and Fadilah (Int J Med Sci, 2025) examining the role of bioactive tripeptides in wound healing and skin regeneration. For KPV, the authors describe reduction of pro-inflammatory cytokines (IL-1β, TNF-α), upregulation of IL-10, and antibacterial activity against MRSA in hydrogel formulations. For GHK-Cu, evidence is summarised for fibroblast migration, collagen and ECM synthesis, angiogenesis, and antimicrobial activity against S. aureus and E. coli. Tripeptides are noted to act through NF-kappaB suppression, ERK and PI3K/Akt signalling, and TGF-β–mediated collagen pathways. Key limitations highlighted include rapid proteolytic degradation in vivo, low skin penetration, and a sparse human clinical trial base, with most evidence derived from in vitro or rodent models.
Tripeptide K(D)PT Is Well Tolerated in Mild-to-moderate Ulcerative Colitis: Results from a Randomized Multicenter Study
Multicenter, randomized, double-blind, placebo-controlled phase IIa trial (Kucharzik and colleagues, Inflammatory Bowel Diseases 2017) of add-on oral K(D)PT — the tripeptide Lys-D-Pro-Thr, a protease-stabilized derivative of the alpha-MSH C-terminal sequence and a close analogue of KPV — in patients with mild-to-moderate active ulcerative colitis already on baseline therapy. Patients received K(D)PT at 20, 50, or 100 mg twice daily or placebo; the primary endpoint was time to a sustained 50%-or-greater improvement in colitis activity index by week 8. K(D)PT was well tolerated with a safety profile comparable to placebo, and the pooled active group showed higher remission rates at weeks 2 and 4 and greater colitis-activity-index improvement at week 8, though the study was modest in size. This is the closest human controlled evidence in the alpha-MSH(11-13) tripeptide family — but it tests K(D)PT, not KPV itself; no completed randomized trial of KPV in humans exists.
Evaluation of Research Grade Peptides Marketed Directly to Consumers Reveals Extensive Variability in Purity and Measured Abundance
Analysis (Mendias and Awan, preprint, 2026) of 6,441 gray-market peptide samples across fourteen compounds — including ipamorelin, BPC-157, CJC-1295, GHK-Cu, PT-141, retatrutide, semaglutide, sermorelin, TB-500, tesamorelin, and tirzepatide. Applying two quality-acceptance frameworks, between 41.6% and 71.1% of samples failed to meet basic quality criteria, and about 15% showed measurable endotoxin contamination. The study quantifies how often directly-marketed "research grade" peptides miss purity and content benchmarks — a central safety concern for any non-pharmaceutical source.