KPV

KPV is a naturally occurring tripeptide composed of three amino acids: lysine (K), proline (P), and valine (V). It corresponds to amino acid positions 11 through 13 at the C-terminus of alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from proopiomelanocortin (POMC) that plays a central role in immune regulation, pigmentation, and inflammation ^(1,2).

The discovery that such a small fragment of alpha-MSH retained significant anti-inflammatory potency was a landmark finding in melanocortin peptide research. Work by Catania, Lipton, and their collaborators systematically tested fragments of alpha-MSH and identified that the C-terminal KPV sequence carried the anti-inflammatory activity. In contrast, the core melanocortin receptor-binding sequence (His-Phe-Arg-Trp at positions 6-9) was responsible for pigmentation and receptor-mediated hormonal effects ^(1,2,5). This separation means that KPV reduces inflammation without triggering tanning, pigmentation changes, or the broader hormonal effects associated with full-length alpha-MSH or related melanocortin peptides such as Melanotan 2.

At just 342 Daltons, KPV is among the smallest bioactive peptides in the research catalog. This small size gives it unusual pharmacokinetic properties: it can cross intestinal epithelial barriers intact via the PepT1 transporter, making it one of the few research peptides with demonstrated oral bioavailability in preclinical models ⁽³⁾. KPV is not FDA-approved and has no completed human clinical trials for any therapeutic indication. All Healius Peptides KPV is sold strictly for in vitro research purposes.

KPV’s anti-inflammatory mechanism operates through intracellular signaling (also spelled signaling) pathways rather than through classical melanocortin receptor activation. This distinction is critical and has been confirmed in multiple studies.

NF-kB Pathway Inhibition

The primary target of KPV is nuclear factor kappa-B (NF-kB), the master transcription factor that controls the expression of pro-inflammatory genes. When cells are exposed to inflammatory stimuli (TNF-alpha, IL-1beta, lipopolysaccharide), NF-kB translocates from the cytoplasm to the nucleus and activates transcription of inflammatory cytokines, adhesion molecules, and chemokines. KPV inhibits this nuclear translocation at nanomolar concentrations, effectively dampening the inflammatory cascade at its source ^(1,3,5). In parallel, KPV inhibits mitogen-activated protein kinase (MAPK) signaling, providing a second line of anti-inflammatory activity downstream of the initial NF-kB block ⁽³⁾.

PepT1 Transporter-Mediated Uptake

A 2008 study published in Gastroenterology by Dalmasso et al. demonstrated that KPV’s anti-inflammatory effect is mediated through the PepT1 transporter (H+-coupled oligopeptide transporter), not through melanocortin receptors ⁽³⁾. PepT1 is normally expressed in the small intestine and is upregulated in the colon during inflammatory bowel disease. KPV is transported into intestinal epithelial cells and immune cells (including T cells) via PepT1, where it exerts its intracellular anti-inflammatory effects ⁽³⁾. This PepT1-mediated uptake is particularly relevant for oral administration, as it provides a direct transport mechanism from the gut lumen into inflamed colonic tissue.

Not Melanocortin Receptor-Mediated

Multiple studies have confirmed that KPV does not bind melanocortin receptors MC1R, MC3R, or MC5R, does not compete with alpha-MSH for receptor binding, and does not increase intracellular cAMP (the hallmark of melanocortin receptor activation) ^(2,3). Its anti-inflammatory activity is retained in mice with nonfunctional MC1R receptors ⁽²⁾. This receptor independence is what allows KPV to deliver anti-inflammatory effects without the pigmentation, sexual function, or appetite effects associated with melanocortin receptor agonists.

Selective Cytokine Modulation

KPV reduces inflammation by suppressing pro-inflammatory cytokine production rather than by boosting anti-inflammatory cytokine production. Experimental data show significant reductions in IL-1beta, IL-6, IL-12, TNF-alpha, and IFN-gamma in murine colitis models, while the anti-inflammatory cytokine IL-10 remains unchanged ^(3,4). This selective dampening of the inflammatory signal, without broadly altering immune balance, distinguishes KPV from immunosuppressive drugs that carry risks of infection and immune deficiency with long-term use.

Inflammatory Bowel Disease and Colitis

This is the strongest and most extensively characterized (also spelled characterized) research application for KPV. In the Dalmasso et al. study, oral administration of KPV significantly reduced the severity of both DSS-induced and TNBS-induced colitis in mice, as measured by decreased body weight loss, reduced mucosal damage, and lower pro-inflammatory cytokine mRNA expression ⁽³⁾. The effective dose used (100 micromolar KPV in drinking water) was based on established alpha-MSH colitis protocols ^(6,7). Follow-up research by Xiao et al. demonstrated that oral delivery of KPV via hyaluronic acid-functionalized nanoparticles further enhanced its anti-colitis efficacy, yielding even greater reductions in mucosal inflammation and TNF-alpha expression ⁽⁴⁾.

Colitis-Associated Cancer

A 2016 study by Viennois et al. published in Cellular and Molecular Gastroenterology and Hepatology investigated the role of PepT1 in colitis-associated cancer (CAC) and the therapeutic potential of KPV. Oral KPV administration prevented carcinogenesis in wild-type mice subjected to inflammation-driven tumor (also spelled tumor) models, reducing tumor number, tumor size, epithelial proliferation, and inflammatory burden ⁽⁸⁾. These anti-tumor effects were PepT1-dependent: when administered to PepT1-knockout mice, KPV did not produce the same inhibitory effects on tumourigenesis, confirming the transporter’s essential role in KPV’s mechanism of action ⁽⁸⁾.

Skin Inflammation and Wound Healing

Alpha-MSH and its C-terminal fragment KPV have demonstrated anti-inflammatory activity in animal models of contact dermatitis, cutaneous vasculitis, and skin wound healing ^(2,5). KPV reduces NF-kB-driven inflammatory gene expression in keratinocytes and endothelial cells, lowers nitric oxide production, and decreases TNF-alpha secretion in activated macrophages ^(1,5). Studies using electrical cell-substrate impedance sensing (ECIS) showed that KPV-containing nanoparticle formulations promoted dose-dependent wound closure in epithelial cell layers ⁽⁴⁾. These findings position KPV as a research tool for dermatological inflammation and wound repair models.

Broader Anti-Inflammatory Applications

Preclinical literature on alpha-MSH-derived peptides has documented anti-inflammatory effects across a wide range of models, including allergic airway inflammation (asthma models), rheumatoid arthritis, ocular inflammation, and brain inflammation ^(2,5). In most of these models, the anti-inflammatory activity of full-length alpha-MSH could be attributed primarily to its C-terminal KPV sequence, making KPV the “active fragment” responsible for the parent hormone’s immune-modulating effects ⁽²⁾. In neuroinflammation research, alpha-MSH peptides have been shown to inhibit nitric oxide and TNF-alpha production by activated microglial cells, and KPV’s ability to cross biological barriers due to its small size makes it a candidate for studying NF-kB-driven neuroinflammatory processes ⁽⁵⁾. The breadth of these preclinical applications reflects the central role NF-kB plays across virtually all inflammatory disease models, and KPV’s targeted inhibition of this pathway gives it relevance well beyond the gut and skin research for which it is best known.

KPV’s small molecular size (342 Da) and stability give it unusual flexibility across administration routes, a characteristic that most larger peptides do not share.

Subcutaneous Injection

Injectable administration delivers KPV directly into systemic circulation. This is the standard route for most research peptides and ensures complete bioavailability. Healius Peptides supplies KPV as a lyophilized powder for reconstitution with bacteriostatic water, supporting injectable research protocols.

Oral Administration

Oral delivery is where KPV distinguishes itself from the vast majority of research peptides. The Dalmasso et al. study demonstrated that KPV added to drinking water was effective in reducing colitis severity in mice ⁽³⁾. This oral efficacy is mediated by PepT1 transport: the transporter actively absorbs KPV from the gut lumen into inflamed epithelial and immune cells, concentrating the peptide precisely where it is needed most in gut inflammation models. Advanced oral delivery systems, including hyaluronic acid-functionalized nanoparticles and polysaccharide hydrogel encapsulation, have been developed to further enhance KPV’s oral bioactivity and colonic targeting ⁽⁴⁾.

Topical Application

KPV has been investigated in topical formulations (creams, gels) for research on skin inflammation. Its small size enables penetration through skin barriers, and its NF-kB inhibitory activity is relevant to dermatitis, eczema, psoriasis, and wound-healing models. Topical KPV formulations have not shown significant irritation or adverse local reactions in preclinical testing ⁽⁹⁾. Immobilized KPV preparations (covalently attached to polymer beads via PEG linkers) have also been developed for localized anti-inflammatory delivery research ⁽¹⁰⁾.

Healius Peptides supplies KPV as a 5mg lyophilized powder in a sealed, sterile vial. Reconstitution requires bacteriostatic water (BAC water).

Reconstitution

Draw the desired volume of BAC water into a sterile syringe. Insert the needle through the vial stopper and direct the stream gently down the inside wall of the vial. Do not aim directly at the lyophilized pellet. Allow the powder to dissolve naturally; gently swirl if needed, but do not shake. The resulting solution should be clear before use. Use our KPV dosage calculator to determine the correct reconstitution volume for your target concentration.

Research Dosage Ranges

There are no established human clinical dosing guidelines for KPV, as no therapeutic trials have been completed. In the published preclinical literature, oral dosing in murine colitis models used 100 micromolar concentrations in drinking water ⁽³⁾. Injectable research protocols commonly reference doses in the 200-500 microgram range per administration ⁽⁹⁾. Community-reported protocols typically suggest once- or twice-daily administration, with some noting a preference for morning or bedtime dosing depending on the measured research endpoints.

Storage

Store unreconstituted KPV at -20°C for long-term stability. Once reconstituted with BAC water, store the vial at 2 to 8°C (standard refrigerator temperature) and use within 21 to 30 days. Avoid repeated freeze-thaw cycles. Protect from direct light.

1. 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. Alpha-MSH anti-inflammatory effects mediated by NF-kB suppression. C-terminal tripeptide KPV retains anti-inflammatory potency. Effects on TNF-alpha, IL-6, and nitric oxide production. Multiple cell types and inflammation models were reviewed.

2. Brzoska T, Luger TA, Maaser C, et al. Alpha-MSH-related peptides: a new class of anti-inflammatory and immunomodulating drugs. Annals of the Rheumatic Diseases. 2008;67(Suppl 3):iii46-iii52. KPV retains anti-inflammatory activity in mice with nonfunctional MC1R. KPV does not bind MC1,3,5R. Anti-inflammatory effects in models of colitis, dermatitis, vasculitis, asthma, arthritis, ocular, and brain inflammation—C-terminal tripeptide as active fragment of alpha-MSH.

3. Dalmasso G, Charrier-Hisamuddin L, Thu Nguyen HT, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. Landmark study. PepT1, not melanocortin receptors, mediates KPV’s anti-inflammatory effect. Nanomolar KPV inhibits NF-kB and MAPK signaling. Oral KPV reduces DSS- and TNBS-induced colitis in mice. PepT1 is upregulated in the colon during IBD. KPV is transported into immune and epithelial cells.

4. Xiao B, Laroui H, 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. HA-functionalized nanoparticles enhanced oral KPV delivery. Reduced mucosal damage and TNF-alpha expression in colitis models. Dose-dependent wound closure in epithelial cell ECIS assays.

5. Luger TA, Scholzen TE, Brzoska T, Bohm M. New insights into the functions of alpha-MSH and related peptides in the immune system. Annals of the New York Academy of Sciences. 2003; 994:133-140. Alpha-MSH and KPV effects on NF-kB in keratinocytes and endothelial cells. Nitric oxide and TNF-alpha suppression. Anti-inflammatory activity across dermatological and immunological models.

6. Rajora N, Boccoli G, Catania A. Alpha-MSH modulates experimental inflammatory bowel disease. Peptides. 1997; 18:381-385. Early demonstration of alpha-MSH anti-inflammatory activity in colitis models—basis for KPV dosing protocols in subsequent studies.

7. Oktar BK, Ercan F, Yegen BC. The effect of alpha-melanocyte-stimulating hormone on colonic inflammation in the rat. Peptides. 2000; 21:1271-1277. Alpha-MSH reduces colonic inflammation in the trinitrobenzene sulphonic acid model. Supporting evidence for melanocortin-derived peptide anti-inflammatory effects in the GI tract.

8. Viennois E, Ingersoll SA, Ayyadurai S, et al. Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory tripeptide KPV in a murine model. Cellular and Molecular Gastroenterology and Hepatology. 2016;2(3):340-357. Oral KPV prevented colitis-associated carcinogenesis in wild-type mice: reduced tumor number, size, epithelial proliferation, and inflammatory burden. Effects abolished in PepT1-knockout mice. PepT1 is upregulated in human colorectal cancer biopsies.

9. KPV preclinical safety and dosing documentation. Well tolerated across oral, injectable, and topical routes in animal models—no significant systemic toxicity. Topical formulations showed no meaningful irritation. Community-reported doses in the 200-500 microgram range for injectable protocols. Mild transient GI discomfort at higher oral doses is the most commonly noted effect.

10. Immobilized alpha-MSH 10-13 (GKPV) inhibits TNF-alpha-stimulated NF-kB activity. GKP-d-V is covalently attached to polymer beads via a PEG linker. Localized anti-inflammatory delivery demonstrating retained NF-kB inhibitory activity of immobilized KPV-containing sequences.

11. BPC-157 mechanism overview. Body Protection Compound-157, pentadecapeptide. Promotes angiogenesis (VEGF, EGF, FGF upregulation), gastric cytoprotection, tissue repair across multiple organ systems. Oral stability is documented in animal models—a complementary mechanism to KPV’s anti-inflammatory NF-kB inhibition.

This product is intended for laboratory research use only. It is not a drug, food, cosmetic, or dietary supplement, and it is not intended for human or veterinary consumption. KPV (Lysine-Proline-Valine) has not been approved by the U.S. Food and Drug Administration or any other regulatory agency for any therapeutic indication. All information provided in this document is drawn from published, peer-reviewed scientific literature and is intended solely to support researchers in designing and interpreting in vitro studies. Healius Peptides makes no claims regarding the safety, efficacy, or suitability of this product for any use other than laboratory research. Buyers accept full responsibility for ensuring their use complies with all applicable local, state, federal, and international regulations.