KPV
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Research Use Only
These products are for laboratory research only and not intended for medical use. They are not FDA-approved to diagnose, treat, cure, or prevent any disease. By purchasing, you certify they will be used solely for research and not for human or animal consumption.
Research Summary
26 PubMed CitationsOverview KPV (Lys-Pro-Val) is a naturally occurring tripeptide derived from the C-terminal fragment (amino acids 11–13) of alpha-melanocyte-stimulating hormone (α-MSH), a 13-amino acid POMC-derived neuropeptide.[1][2] Originally characterized by James M. Lipton and Melanie E. Hiltz in 1989, KPV was identified as the specific molecular fragment responsible for the parent hormone's anti-inflammatory and antipyretic activities — the "active message sequence" that retains immunomodulatory and antimicrobial properties while lacking pigment-inducing activity.[7][8] A critical mechanistic distinction: KPV does not bind melanocortin receptors (MC1R-MC5R) in mammalian cells, does not increase cAMP, and does not induce melanogenesis. Instead, it enters cells via the PepT1 (SLC15A1) oligopeptide transporter — which is notably upregulated in inflamed colonic tissue — enabling targeted delivery to sites of active inflammation.[3][4] The FDA placed KPV on the Category 2 Bulk Drug Substances list, citing insufficient human exposure data and potential immunogenicity from peptide-related impurities.[5] No large-scale randomized controlled trials have been...
KPV — Research Data at a Glance
| Property | Value |
|---|---|
| PubMed Citations Referenced | 26 |
| Contributing Researchers | 3 |
| Storage Conditions | Store lyophilized KPV at −20°C for 2–3 years; reconstituted at 2–8°C for 7–14 days. |
| Purity Standard | ≥99% (HPLC verified, 3rd-party COA) |
| Research Use Only | Not for human consumption. RUO only. |
Overview
Overview
KPV (Lys-Pro-Val) is a naturally occurring tripeptide derived from the C-terminal fragment (amino acids 11–13) of alpha-melanocyte-stimulating hormone (α-MSH), a 13-amino acid POMC-derived neuropeptide.[1][2]
Originally characterized by James M. Lipton and Melanie E. Hiltz in 1989, KPV was identified as the specific molecular fragment responsible for the parent hormone's anti-inflammatory and antipyretic activities — the "active message sequence" that retains immunomodulatory and antimicrobial properties while lacking pigment-inducing activity.[7][8]
A critical mechanistic distinction: KPV does not bind melanocortin receptors (MC1R-MC5R) in mammalian cells, does not increase cAMP, and does not induce melanogenesis. Instead, it enters cells via the PepT1 (SLC15A1) oligopeptide transporter — which is notably upregulated in inflamed colonic tissue — enabling targeted delivery to sites of active inflammation.[3][4]
The FDA placed KPV on the Category 2 Bulk Drug Substances list, citing insufficient human exposure data and potential immunogenicity from peptide-related impurities.[5] No large-scale randomized controlled trials have been published; human data is limited to patent case studies (psoriasis, contact dermatitis).[9]
Mechanism of Action
Mechanism of Action
PepT1-Mediated Cellular Entry (Primary Mechanism)
Unlike its parent α-MSH — which acts through G-protein coupled melanocortin receptors (MC1R–MC5R) — KPV enters cells via the proton-coupled oligopeptide transporter PepT1 (SLC15A1). In human intestinal epithelial cells (Caco2-BBE), PepT1 transports KPV with a Km of ~160 µM; in Jurkat T-cells, Km ≈ 700 µM.[3][4]
Importin-α3 Binding (Intracellular Target)
Once internalized, KPV binds Importin-α3 (Imp-α3) at armadillo domains 7–8, physically blocking the nuclear import of NF-κB p65RelA — preventing it from entering the nucleus to transcribe pro-inflammatory genes.[10][11]
NF-κB Pathway Inhibition (Dual Mechanism)
KPV inhibits NF-κB through two complementary actions: (1) stabilizing IκBα by preventing its phosphorylation and degradation, and (2) blocking p65RelA nuclear translocation via Importin-α3 binding. This dual mechanism provides robust suppression of inflammatory gene transcription at concentrations as low as 10 nM.[10][12]
MAPK Pathway Inhibition
KPV inhibits phosphorylation and activation of three major MAP kinases: ERK1/2, JNK, and p38 — reducing pro-inflammatory cytokine production induced by TNFα and other stimuli.[13]
mTORC1 Activation
KPV activates mTORC1 (mechanistic target of rapamycin complex 1), evidenced by increased phosphorylation of p70 S6K at T389 — suggesting a role in translational control and cell growth recovery during inflammation.[14]
Calcium Signaling (Keratinocytes)
In human keratinocytes, KPV elevates intracellular Ca²⁺ concentrations via an adenosine agonist-dependent pathway — distinct from the cAMP pathway used by α-MSH in other tissues.[14]
α-MSH vs. KPV: Key Distinctions
| Feature | α-MSH (Parent) | KPV (Fragment) |
|---|---|---|
| Structure | 13 amino acids (tridecapeptide) | 3 amino acids (C-terminal tripeptide) |
| Primary Entry | Binds MC1R–MC5R (cell surface) | Transported by PepT1 (intracellular) |
| Second Messenger | Increases cAMP | Does NOT increase cAMP; ↑ Ca²⁺ in keratinocytes |
| Pigmentation | Induces melanogenesis | No pigmentation effect |
| Inflammation | Inhibits IκBα degradation | Inhibits IκBα + blocks p65 nuclear import via Importin-α3 |
Research Applications
Research Applications
KPV demonstrates potent anti-inflammatory activity across diverse tissue models, with unusually favorable therapeutic index given its nanomolar potency:
- Inflammatory Bowel Disease / Colitis — Oral KPV in drinking water reduces DSS/TNBS-induced colitis (MPO reduced ~50%, weight loss attenuated). HA-nanoparticle delivery achieves 12,000-fold potency increase over free peptide. PepT1-dependent mechanism confirmed in KO mice.[3][6][15]
- Dermatological Inflammation — Topical KPV reduces psoriasis symptoms (>8 hours relief vs 3 hours hydrocortisone), atopic/contact dermatitis without skin atrophy or steroid side effects. Patent case studies document human efficacy.[9][16]
- Corneal and Cutaneous Wound Healing — Accelerated re-epithelialization in rabbit corneal wounds (topical, 4x daily) and oral mucositis (KPV@PPP_E hydrogel) with tissue morphology restoration.[17][18]
- Antimicrobial Activity — Active against S. aureus and C. albicans at picomolar to micromolar range. Dimeric form [CKPV]₂ shows enhanced candidacidal activity.[19][20]
- Arthritis and Joint Inflammation — Reduced joint swelling, cartilage destruction, and PMN leukocyte infiltration in crystal-induced peritonitis models.[21]
- Pulmonary Inflammation — Inhibits MMP-9 activity, reduces eotaxin and IL-8 secretion in bronchial epithelial cells exposed to TNFα or RSV.[22]
- Colitis-Associated Cancer — KPV prevented AOM/DSS-induced carcinogenesis in WT mice but not PepT1-KO mice, confirming PepT1-dependent anti-tumorigenic mechanism.[23]
- Vascular Calcification — Self-assembled KPV/rapamycin nanodrugs inhibit vascular calcification via anti-inflammatory + autophagy pathways.[24]
Biochemical Characteristics
| Property | Value |
|---|---|
| Molecular Formula | C₁₆H₃₀N₄O₄ |
| Molecular Weight | 342.44 g/mol (378.47 for Ac-KPV-NH₂) |
| CAS Number | 107715-88-8 |
| Sequence (3-Letter) | Lys-Pro-Val |
| Sequence (1-Letter) | KPV |
| Amino Acids | 3 (linear tripeptide) |
| Structural Type | Linear tripeptide; often synthesized with N-acetylation and C-terminal amidation (Ac-KPV-NH₂) |
| Parent Molecule | α-MSH (alpha-melanocyte-stimulating hormone), amino acids 11–13 |
| Synonyms | α-MSH(11-13), alpha-melanocyte-stimulating hormone (11-13), KPV peptide |
| Plasma Half-Life | <30 minutes |
Identifiers
| InChI Key | |
|---|---|
| Isomeric SMILES | |
| Purity Standard | |
| Endotoxin | |
| Water Content |
Preclinical Research Summary
Preclinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Dalmasso et al. (2008) | C57BL/6 mice — DSS + TNBS colitis | 100 µM KPV oral: MPO reduced ~50% (DSS); weight loss 5–10% vs 15–20% control (p < 0.05); PepT1-mediated uptake confirmed | [3] |
| Kannengiesser et al. (2008) | Mice — DSS + MC1R-KO | KPV rescued MC1Re/e mice from death in DSS colitis → mechanism is MC1R-independent | [15] |
| Xiao et al. (2017) | FVB mice — HA-KPV-NPs oral | 16 µg/kg/day × 6 days: 12,000-fold lower dose vs free KPV with equivalent efficacy; MPO to healthy-control levels (p < 0.01) | [6] |
| Viennois et al. (2016) | WT/PepT1-KO mice — AOM/DSS | KPV prevented colitis-associated cancer in WT but NOT PepT1-KO → PepT1 dependence confirmed for anti-tumorigenic effects | [23] |
| Bonfiglio et al. (2006) | Rabbits — corneal wounds | Topical KPV 4x daily × 4 days: significantly smaller corneal wounds vs control | [17] |
| Shao et al. (2022) | Rats — oral mucositis + MRSA | KPV@PPP_E hydrogel: ↓ IL-1β, TNF-α; ↑ IL-10; restored gingival tissue morphology; dual anti-inflammatory + antibacterial | [18] |
Human Data (Patent Case Studies)
| Case | n= | Result | Ref |
|---|---|---|---|
| Psoriasis (US 6,894,028) | 1 | 1 mg topical KPV: symptom relief >8 hours/application (vs 3 hours hydrocortisone); no AEs (hydrocortisone → telangiectasia/atrophy) | [9] |
| Contact Dermatitis (US 6,894,028) | 1 | Topical KPV: marked improvement within minutes; symptoms did not return | [9] |
Dose-Response Parameters
| Parameter | Value | Ref |
|---|---|---|
| Anti-inflammatory IC (NF-κB/MAPK) | 10 nM | [3] |
| Antimicrobial range | Picomolar to micromolar | [19] |
| PepT1 Km (intestinal cells) | ~160 µM | [3] |
| PepT1 Km (T-cells) | ~700 µM | [4] |
| Oral dose (murine colitis) | 100 µM in drinking water | [3] |
| HA-NP dose (12,000x potency) | 16 µg/kg/day oral | [6] |
| Plasma half-life | <30 minutes | [25] |
| Acute toxicity (LD50) | Not identified (>100 mg/kg) | [25] |
The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
Authors & Attribution
✍️ Article Author
Dr. James M. Lipton
James M. Lipton, PhD, is a pioneering researcher affiliated with Zengen Inc. and the University of Texas. Lipton is the lead inventor who established that the anti-inflammatory and antipyretic activities of the larger α-MSH hormone reside specifically in its C-terminal tripeptide sequence, KPV. He demonstrated that KPV exerts efficacy across a broad range of concentrations, including physiological picomolar ranges, and holds multiple patents for its use in treating dermatological disorders, uro-genital conditions, and systemic inflammation. James M. Lipton is being referenced as one of the leading scientists involved in the research and development of KPV. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →🎓 Scientific Journal Author
Dr. Didier Merlin
Didier Merlin, PhD, is affiliated with the Department of Medicine, Division of Digestive Diseases at Emory University School of Medicine, and the Institute for Biomedical Sciences at Georgia State University. Dr. Merlin's research established PepT1-mediated uptake as the primary mechanism of KPV action in intestinal inflammation. His group developed hyaluronic acid-functionalized nanoparticles (HA-KPV-NPs) that achieved a 12,000-fold potency increase in targeted colonic delivery for ulcerative colitis treatment. Didier Merlin is being referenced as one of the leading scientists involved in the research and development of KPV. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →Dr. Didier Merlin is being referenced as one of the leading scientists involved in the research and development of KPV. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
🔬 Contributing Researcher
Dr. Anna Catania
Anna Catania, MD, is affiliated with the Division of Internal Medicine at IRCCS Ospedale Maggiore, Milano, Italy, and is also associated with Zengen Inc. as a patent co-inventor. Dr. Catania has been instrumental in characterizing the antimicrobial and immunomodulatory properties of KPV, demonstrating that KPV and its dimeric forms possess candidacidal and antibacterial properties against Staphylococcus aureus and Candida albicans without the immunosuppressive side effects typical of other anti-inflammatory drugs. Anna Catania is being referenced as one of the leading scientists involved in the research and development of KPV. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →Dr. Anna Catania is being referenced as one of the leading scientists involved in the research and development of KPV. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
Referenced Citations
Sikiric P, et al. A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis. Journal of Physiology-Paris. 1993;87(5):313-327.
DOIBrzoska T, Luger TA, Maaser C, Abels C, Böhm M. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives. Endocrine Reviews. 2008;29(5):581-602.
DOIDalmasso 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.
DOILaroui H, Dalmasso G, Nguyen HT, Yan Y, Sitaraman SV, Merlin D. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010;138:843-853.
DOIU.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. FDA.gov. Updated 2023.
FDA.govXiao B, Xu Z, Viennois E, Zhang Y, Zhang Z, Zhang M, Han MK, Kang Y, Merlin D. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Molecular Therapy. 2017;25(7):1628-1640.
DOIHiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB Journal. 1989;3:2282-2284.
DOILuger 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.
DOILipton JM, Catania AP. Use of KPV tripeptide for dermatological disorders. U.S. Patent No. 6,894,028 B2. 2005.
SourceGetting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. Journal of Pharmacology and Experimental Therapeutics. 2003;306(2):631-637.
DOIKelly JM, Moir AJG, Carlson KE, Haycock JW. Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity. Peptides. 2006;27(3):431-437.
DOILand SC. Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides. International Journal of Physiology, Pathophysiology and Pharmacology. 2012;4(2):59-73.
PubMedElliott RJ, Szabo M, Wagner MJ, Kemp EH, MacNeil S, Haycock JW. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. Journal of Investigative Dermatology. 2004;122(4):1010-1019.
DOISongok AC, Panta P, Doerrler WT, Macnaughtan MA, Taylor CM. Structural modification of the tripeptide KPV by reductive glycoalkylation of the lysine residue. PLOS One. 2018;13(6):e0199686.
DOIKannengiesser 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.
DOIBöhm M, Luger T. Are melanocortin peptides future therapeutics for cutaneous wound healing? Experimental Dermatology. 2019;28:219-224.
DOIBonfiglio V, et al. Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide. Experimental Eye Research. 2006;83(6):1366-1372.
DOIShao W, Chen R, Lin G, Ran K, Zhang Y, Yang J, Xu H. In situ mucoadhesive hydrogel capturing tripeptide KPV: the anti-inflammatory, antibacterial and repairing effect on chemotherapy-induced oral mucositis. Biomaterials Science. 2022;10:227-242.
DOICutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of alpha-MSH peptides. Journal of Leukocyte Biology. 2000;67(2):233-239.
DOICatania A, et al. Three-dimensional structure of the α-MSH-derived candidacidal peptide [Ac-CKPV]2. The Journal of Peptide Research. 2005;66(1):19-26.
DOICharnley M, Moir AJG, Douglas CWI, Haycock JW. Anti-microbial action of melanocortin peptides and identification of a novel X-Pro-d/l-Val sequence in Gram-positive and Gram-negative bacteria. Peptides. 2008;29(6):1004-1009.
DOILand SC, et al. KPV inhibits MMP-9 activity and reduces eotaxin and IL-8 secretion in bronchial epithelial cells. International Journal of Physiology, Pathophysiology and Pharmacology. 2012;4(2):59-73.
PubMedViennois E, et al. Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-inflammatory PepT1-Mediated Tripeptide KPV in a Murine Model. Cellular and Molecular Gastroenterology and Hepatology. 2016;2(3):340-357.
DOIWu Y, et al. KPV and RAPA Self-Assembled into Carrier-Free Nanodrugs for Vascular Calcification Therapy. Advanced Healthcare Materials. 2024.
PubMedCatania A, et al. Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions. The Journal of Surgical Research. 2006;131.
PubMedPawar K, Kolli CS, Rangari NS, Babu RJ. Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin. Journal of Pharmaceutical Sciences. 2017;106(7):1814-1820.
DOIRUO Disclaimer
For Research Use Only (RUO). This product is intended solely for in-vitro research and laboratory experimentation. It is not a drug, food, cosmetic, or medical device and has not been approved by the FDA for any human or veterinary use. It must not be used for therapeutic, diagnostic, or any other non-research purpose. Pure US Peptide does not condone or encourage the use of this product for anything other than strictly defined research applications. Users assume full responsibility for compliance with all applicable regulations and guidelines.
Certificate of Analysis (COA)
Every batch is strictly tested by accredited third-party laboratories (ISO 17025) to ensure 99%+ purity.
Latest Lab Report
Storage & Handling
Summary
Store lyophilized KPV at −20°C for 2–3 years; reconstituted at 2–8°C for 7–14 days. Avoid freeze-thaw cycles. Protect from light/moisture.
Recommended Laboratory Storage Conditions
Lyophilized Powder: Store at −20°C (−4°F) for long-term stability (2–3 years). Protect from light and moisture; use desiccants to prevent moisture absorption. Supplied as acetate or trifluoroacetate salt.
Reconstituted Solution: Refrigerate at 2–8°C (36–46°F). Use within 7–14 days. Dissolves rapidly in sterile or bacteriostatic water to form a clear, colorless solution.
Handling: Standard aseptic technique with personal protective equipment (gloves, lab coat). Avoid repeated freeze-thaw cycles to maintain biological activity.
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