KPV (α-MSH 11-13 Tripeptide)
A cell-permeable tripeptide fragment of alpha-melanocyte stimulating hormone (α-MSH) investigated for anti-inflammatory, antimicrobial, and wound-healing research applications[1], [2].
Key Research Properties:
| SKU: | kpv |
|---|---|
| Purity: | >99% (HPLC Verified) |
| Form: | Lyophilized Powder |
| Storage: | Store at -20°C |
| CAS Number: | 67727-97-3 |
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What is KPV?
KPV (Lys-Pro-Val) is the C-terminal tripeptide of alpha-melanocyte stimulating hormone (α-MSH) that preserves the hormone’s broad anti-inflammatory activity while offering superior metabolic stability and direct intracellular access to inflammatory signaling pathways[1], [2], [3], [4].
Biochemical Properties
- Sequence: Lys-Pro-Val (K-P-V)
- Molecular Weight: 342.43 g/mol
- Structure: Linear tripeptide (3 amino acids)
- Origin: C-terminal fragment of α-MSH (amino acids 11-13)
- Stability: Resistant to proteolytic degradation; supportive of oral and topical formulations
- Membrane Permeability: Cell-penetrating; reaches intracellular inflammatory targets
Primary Functions
- Anti-inflammatory: Inhibits NF-κB and downstream pro-inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β)
- Antimicrobial: Disrupts bacterial and fungal membranes; reduces biofilms
- Wound Healing: Accelerates re-epithelialization and limits scar formation
- Intestinal Health: Restores mucosal integrity and tight junction proteins in colitis models
- Antioxidant: Mitigates oxidative stress and inflammatory damage
Functional properties summarised from preclinical and translational reports on α-MSH 11-13 derivatives[3], [5], [7], [8], [9], [10].
Discovery & Development
KPV was identified during structure–activity studies demonstrating that the α-MSH 11-13 sequence preserved anti-inflammatory potency while reducing peptide length and improving tissue penetration.[1], [3], [4] Subsequent work confirmed direct NF-κB modulation, antimicrobial effects, and broad anti-inflammatory activity across epithelial and immune cell systems.[4], [8]
Key Research Milestones:
- 1989–1997: COOH-terminal α-MSH fragments shown to suppress inflammation and modulate immune responses in vivo[1], [2]
- 2003: NF-κB inhibition and cytokine suppression characterised for KPV and related peptides[4]
- 2004–2013: Robust efficacy demonstrated in DSS/TNBS colitis and other inflammatory disease models[5], [6]
- 2006–2013: Expanded antimicrobial, wound-healing, and neuroprotective research[7], [8], [11]
- 2021–Present: Translational reviews highlight oral and topical formulation strategies for inflammatory and fibrotic disorders[12]
Molecular & Chemical Information
Chemical Structure
KPV (Lys-Pro-Val) α-MSH 11-13 fragment represented as a linear tripeptide backbone[12].
| Property | KPV (α-MSH 11-13) |
|---|---|
| Peptide Sequence | Lys-Pro-Val |
| Molecular Formula | C16H30N4O4 |
| Molecular Weight | 342.43 g/mol |
| CAS Number | 67727-97-3 |
| Structure Class | Linear tripeptide (α-MSH 11-13 fragment) |
| Physicochemical Traits | Water-soluble; amphipathic; resistant to rapid proteolysis |
| Receptor Affinity | Weak agonist at MC1R/MC3R; significant receptor-independent NF-κB modulation |
| First Described | Late 20th century α-MSH truncation studies |
Chemical specifications based on analytical and pharmacologic evaluations of α-MSH fragments[1], [3], [12].
Unique Advantages Over α-MSH
Mechanism of Action
KPV exerts anti-inflammatory effects through direct intracellular inhibition of NF-κB, modulation of melanocortin receptors, and complementary antimicrobial activity enabled by its amphipathic, cell-permeable structure[4], [8].
NF-κB Inhibition (Primary Mechanism)
Direct Intracellular Anti-Inflammatory Action
Nuclear Factor Kappa B (NF-κB): Master transcription factor that drives expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β), chemokines, adhesion molecules, and inflammatory enzymes (COX-2, iNOS).
KPV's NF-κB Inhibition:
- Cell Penetration: KPV crosses cell membranes via its small size and amphipathic properties
- IκB Stabilization: Prevents degradation of IκB (NF-κB inhibitor), keeping NF-κB sequestered in cytoplasm
- Nuclear Translocation Blockade: Reduces NF-κB p65 subunit translocation to nucleus
- DNA Binding Reduction: Decreases NF-κB binding to inflammatory gene promoters
- Result: Significant reductions in pro-inflammatory cytokines across epithelial and immune cell models
Antimicrobial & Anti-Biofilm Activity
Direct Pathogen Killing & Biofilm Disruption
KPV exhibits direct antimicrobial activity independent of its anti-inflammatory effects:
- Bacterial Targets: Staphylococcus aureus, E. coli, Pseudomonas aeruginosa; disrupts bacterial membranes
- Fungal Activity: Effective against Candida albicans
- Biofilm Disruption: Breaks down bacterial biofilms (protective matrices that resist antibiotics)
- Synergy with Antibiotics: Enhances efficacy of conventional antimicrobials
- Mechanism: Membrane disruption via amphipathic structure; inhibition of quorum sensing
Clinical Relevance: Valuable for infected wounds, surgical site infections, and IBD (where dysbiosis and microbial translocation amplify inflammation)[7], [8].
Additional Anti-Inflammatory Mechanisms
Melanocortin Receptor Modulation & More
Beyond NF-κB inhibition, KPV modulates inflammation through:
- Melanocortin Receptors: Weak agonism at MC1R/MC3R complements receptor-independent actions
- IL-10 Induction: Enhances anti-inflammatory IL-10 production by immune cells
- Mast Cell Stabilization: Reduces mast cell degranulation and histamine release
- Oxidative Stress Reduction: Decreases ROS production; enhances antioxidant enzyme activity
- Tight Junction Preservation: Maintains intestinal barrier integrity; prevents “leaky gut”
Research & Evidence
KPV has demonstrated robust activity in preclinical models of inflammatory bowel disease, mucosal barrier injury, cutaneous inflammation, and trauma-related neuroinflammation, supporting its evaluation in oral and topical formulations[5], [6], [9], [11].
Inflammatory Bowel Disease (IBD)
Ulcerative Colitis & Crohn's Disease Models
Primary Research Focus: KPV has shown impressive efficacy in animal models of colitis.
- DSS & TNBS Colitis: Oral or parenteral KPV lowers disease activity, histological injury, and inflammatory cytokines
- Barrier Protection: Preserves tight junction proteins and reduces neutrophil infiltration
- Immune Modulation: Enhances IL-10 while suppressing NF-κB-driven mediators
- Translational Outlook: Oral enteric-coated formulations are under investigation for mucosal delivery
Preclinical IBD findings summarised from murine DSS/TNBS studies and translational formulation assessments[5], [6], [12].
Wound Healing & Dermatology
Topical Applications for Skin Conditions
- Wound Healing: Topical KPV accelerates epithelial closure and limits scar formation
- Ocular Surface Repair: Enhances corneal re-epithelialization following injury
- Dermatitis & Psoriasis Models: Reduces pruritus, edema, and keratinocyte hyperproliferation
- Antimicrobial Barrier: Limits pathogen overgrowth in infected wound models
- Formulation: Stable in gels, creams, and hydrogel dressings
Dermatologic and wound-healing activity documented in murine and rabbit studies of topical α-MSH 11-13 derivatives[8], [9], [10].
Systemic & Neuroprotective Effects
Trauma and Systemic Inflammation Models
- Traumatic Brain Injury: Single-dose α-MSH 11-13 reduces lesion volume and inflammatory apoptosis in murine TBI
- Crystal-Induced Inflammation: Melanocortin peptides dampen neutrophil activation in gout models
- Sepsis-Endotoxin Models: KPV analogs attenuate cytokine storms and improve survival metrics
Systemic protection reported across inflammatory trauma paradigms and innate immune challenge models[11], [13].
Dosing & Administration
Research Protocols
- In Vitro: 1–100 µM in epithelial or immune cell culture; NF-κB inhibition evident at 10–50 µM
- Animal Models (IBD): 0.5–5 mg/kg oral daily; 0.1–1 mg/kg IP/SC to attenuate DSS or TNBS colitis
- Topical (Wound): 0.1–1% KPV in hydrogel or cream formulations applied once or twice daily
- Storage: Lyophilized at -20°C; reconstituted aliquots stable at 4°C ≤7 days
Representative dosing ranges derived from preclinical colitis, wound-healing, and mechanistic studies[5], [6], [9].
Safety & Side Effects
KPV demonstrates excellent tolerability in preclinical studies, with no dose-limiting toxicity observed across systemic, topical, or oral administrations[1], [12].
Preclinical Safety Profile
- Toxicity: No adverse effects at doses 10-100× therapeutic range in animal studies
- Immunogenicity: Low; minimal antibody formation (small peptide)
- Organ Toxicity: No liver, kidney, cardiac toxicity observed
- Local Tolerance: Well-tolerated SC, IP, oral, topical routes
Safety findings compiled from dose-escalation, topical application, and translational reviews of α-MSH fragments[1], [10], [12].
Frequently Asked Questions
Clinical Trials & Development Status
Clinical evaluation of α-MSH-derived peptides, including the KPV (11-13) fragment and full-length analogs, spans ophthalmology, metabolic disease, intestinal permeability, and acute kidney injury indications.[14], [15], [16], [17]
NCT03451578 • Completed (Duke University Eye Center)
Diagnostic single-group study evaluating intraocular α-MSH concentrations in advanced dry macular degeneration.
- Population: 54 adults with advanced dry macular degeneration (Durham, North Carolina, USA)
- Design: Interventional; diagnostic primary purpose; single-group assignment; open-label
- Intervention: Alpha MSH assay (ELISA-based analysis of aqueous humor samples)
- Primary Endpoint: α-MSH concentration measured two hours post-sampling via ELISA
- ClinicalTrials.gov: NCT03451578
Assesses ocular fluid α-MSH dynamics as a biomarker for retinal degenerative disease[14].
NCT06293664 • Recruiting (Dasman Diabetes Institute)
Randomized, quadruple-masked crossover study testing α-MSH infusion during oral glucose tolerance testing in adults with Type 2 diabetes.
- Population: 13 participants with Type 2 Diabetes Mellitus (Kuwait City, Kuwait)
- Design: Interventional; randomized crossover; quadruple-masked; screening primary purpose
- Interventions: Intravenous α-MSH infusion versus placebo (0.5% human albumin in saline)
- Primary Endpoint: Difference in total/incremental AUC for glucose and insulin during OGTT across infusion arms (12-month window)
- Secondary Outcomes: Metabolite AUCs (C-peptide, glucagon, gut hormones, α-MSH), energy intake during ad libitum meal test, adverse events
- ClinicalTrials.gov: NCT06293664
Explores whether α-MSH improves glucose disposal and metabolic flexibility in T2DM[15].
NCT02170467 • Completed (University Hospital, Rouen)
Parallel-assignment study comparing intestinal permeability and α-MSH autoantibodies in anorexia nervosa before and after refeeding.
- Population: 69 participants (23 anorexia nervosa patients, 46 healthy controls) in Rouen and Bois-Guillaume, France
- Design: Interventional; non-randomized; parallel assignment; open-label; other primary purpose
- Interventions: Oral lactulose/mannitol/sucralose tests with urinary excretion analysis; α-MSH autoantibody assays
- Primary Endpoint: Percentage of sugar urinary excretion (Day 1–17, following 10% weight gain during refeeding)
- Secondary Outcomes: Sucralose urinary sampling for colonic permeability; evolution of α-MSH autoantibody titers
- ClinicalTrials.gov: NCT02170467
Investigates gut barrier disruption and melanocortin autoimmunity in eating disorders[16].
NCT00004496 • Completed Phase 1 (University of Texas)
Double-blind, placebo-controlled dose-escalation trial assessing α-MSH safety in acute renal failure and post-transplant patients.
- Population: 45 adults with established or high-risk acute renal failure (Dallas, Texas, USA)
- Design: Phase 1 interventional study; dose-escalation cohorts; double-blind; placebo-controlled; treatment primary purpose
- Intervention: Intravenous α-MSH infused over five minutes at escalating dose levels
- Primary Endpoints: Maximum tolerated dose, safety/tolerability profile, pharmacokinetics (including IL-10 modulation)
- ClinicalTrials.gov: NCT00004496
Provides foundational safety data for systemic α-MSH analog administration in critical care settings[17].
References & Scientific Citations
Research Integrity:
All claims are backed by peer-reviewed scientific literature.
- Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide α-MSH. FASEB J. 1989;3(11):2282-2284. PMID: 2676850
- Lipton JM, Catania A. Antiinflammatory actions of the neuroimmunomodulator α-MSH. Immunol Today. 1997;18(3):140-145. doi:10.1016/S0167-5699(97)01009-8
- Luger TA, Brzoska T. α-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Ann Rheum Dis. 2007;66(Suppl 3):iii52-iii55. PMID: 17934096
- Kelly JM, Moir AJG, Carlson K, Yang Y, MacNeil S. Immobilized α-melanocyte stimulating hormone 10–13 (GKPV) inhibits TNF-α stimulated NF-κB activity. Peptides. 2006;27(7):1440-1447. PMID: 16458316
- Kannengiesser K, Maaser C, Heine M, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. PMID: 18092342
- Colombo G, Travelli C, Porta C, et al. Treatment of murine colitis with the tripeptide KPV is associated with modulation of IL-10 and NF-κB. Peptides. 2013;50:117-126. PMID: 24184594
- Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of α-MSH peptides. J Leukoc Biol. 2000;68(5):693-699. doi:10.1189/jlb.68.5.693
- Reddy VB, Kaul KL, He S, et al. Antimicrobial and anti-inflammatory activity of KPV peptide. J Invest Dermatol. 2013;133(S1):S231. doi:10.1038/jid.2013.184
- Bonfiglio V, Camillieri G, Avitabile T, Leggio GM, Anfuso CD, Lupo G. Effects of the COOH-terminal tripeptide α-MSH11–13 on corneal epithelial wound healing: role of nitric oxide. Exp Eye Res. 2006;83(1):149-157. doi:10.1016/j.exer.2006.01.027
- Auriemma M, Brzoska T, Luger T, Loser K. The anti-inflammatory effect of alpha-MSH in skin: a promise for new treatment strategies. Anti-Inflamm Anti-Allergy Agents Med Chem. 2009;8(1):81-86. doi:10.2174/187152309787158411
- Schaible EV, Steinsträßer A, Jahn-Eimermacher A, et al. Single administration of tripeptide α-MSH(11–13) attenuates brain damage after experimental traumatic brain injury in mice. PLoS One. 2013;8(7):e71056. doi:10.1371/journal.pone.0071056
- Dinparastisaleh R, Mirsaeidi M. Antifibrotic and anti-inflammatory actions of α-melanocyte stimulating hormone: new roles for an old player. Pharmaceuticals. 2021;14(1):45. doi:10.3390/ph14010045
- Capsoni F, Ongari AM, Reali E, et al. Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells. Arthritis Res Ther. 2009;11(1):R35. doi:10.1186/ar2827
- ClinicalTrials.gov. Alpha MSH in Ocular Disease. Identifier: NCT03451578. Updated December 22, 2022. https://clinicaltrials.gov/study/NCT03451578
- ClinicalTrials.gov. Protocol for Alpha MSH Infusion Study in Patients With Type 2 Diabetes (α-MSH & T2DM). Identifier: NCT06293664. Updated March 5, 2024. https://clinicaltrials.gov/study/NCT06293664
- ClinicalTrials.gov. Study of Intestinal Permeability in Patients With Anorexia Nervosa (PIANO). Identifier: NCT02170467. Updated October 24, 2019. https://clinicaltrials.gov/study/NCT02170467
- ClinicalTrials.gov. Phase I Study of Alpha-Melanocyte Stimulating Hormone in Patients With Acute Renal Failure. Identifier: NCT00004496. Updated March 25, 2015. https://clinicaltrials.gov/study/NCT00004496
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All products sold by Vital Healer Labs are for laboratory research use only.
Not for human consumption, medical, or veterinary use.