Research Applications
Inflammatory Bowel Disease (IBD)
KPV's most promising application is in IBD (Crohn's disease and ulcerative colitis). Preclinical studies demonstrate oral KPV reduces colonic inflammation, improves mucosal healing, and normalizes inflammatory cytokine levels in colitis models. Its PepT1-mediated intestinal absorption enables effective oral delivery directly to inflamed intestinal tissue.
Gut Inflammation and Permeability
Research shows KPV preserves intestinal barrier integrity by maintaining tight junction proteins (ZO-1, occludin, claudins) and reducing epithelial permeability. This "leaky gut" prevention mechanism has broad implications for gut health.
Skin Inflammation
KPV demonstrates anti-inflammatory effects in dermatological conditions including dermatitis, psoriasis, and wound inflammation. Topical formulations show efficacy in reducing erythema, edema, and inflammatory cell infiltration.
Arthritis and Joint Inflammation
Preclinical studies show KPV reduces joint inflammation and cartilage destruction in arthritis models through NF-κB and inflammasome suppression in synovial tissue.
Neuroinflammation
KPV crosses the blood-brain barrier and reduces neuroinflammation in preclinical models. Research suggests potential applications in multiple sclerosis, Alzheimer's disease, and other neuroinflammatory conditions.
Post-Surgical Inflammation
KPV's potent anti-inflammatory activity without immunosuppression makes it a candidate for reducing post-surgical inflammation while preserving wound healing and antimicrobial defense.
Mechanism of Action
Direct NF-κB Inhibition
KPV's primary anti-inflammatory mechanism is direct inhibition of the NF-κB signaling pathway. It enters cells and interacts with IκB kinase (IKK) complex, preventing IκBα phosphorylation and degradation. This traps NF-κB in the cytoplasm, preventing its nuclear translocation and subsequent transcription of pro-inflammatory genes (TNF-α, IL-1β, IL-6, IL-8, iNOS, COX-2).
Receptor-Independent Mechanism
Unlike full-length α-MSH, which signals through melanocortin receptors (MC1R-MC5R), KPV does not bind melanocortin receptors at appreciable affinity. Instead, it enters cells through peptide transporters (PepT1 in intestinal epithelium) and exerts its anti-inflammatory effects intracellularly. This receptor-independent mechanism is unique among anti-inflammatory peptides.
PepT1-Mediated Intestinal Uptake
KPV is actively transported across intestinal epithelium by the proton-coupled oligopeptide transporter PepT1 (SLC15A1). This enables oral bioavailability — rare for peptide therapeutics. Once inside enterocytes, KPV suppresses local inflammatory signaling, making it particularly effective for intestinal inflammation.
Inflammasome Suppression
KPV inhibits NLRP3 inflammasome assembly and activation, reducing caspase-1 activity and IL-1β/IL-18 maturation. This mechanism is particularly relevant to IBD and other chronic inflammatory conditions driven by inflammasome hyperactivation.
Immune Cell Modulation
KPV suppresses pro-inflammatory activation of macrophages, dendritic cells, and T-cells without causing general immunosuppression. It selectively reduces inflammatory cytokine production while preserving antimicrobial immune function.
Biological Pathways
IKK/NF-κB Inflammatory Cascade
KPV inhibits IKKα/β, preventing IκBα phosphorylation at Ser32/36. Non-phosphorylated IκBα remains bound to NF-κB(p65/p50), sequestering it in the cytoplasm. This blocks transcription of hundreds of NF-κB-dependent pro-inflammatory genes.
MAPK/AP-1 Pathway
KPV also suppresses p38 MAPK and JNK activation, reducing AP-1 transcription factor activity. This provides a second anti-inflammatory mechanism independent of NF-κB, targeting a complementary set of inflammatory genes.
NLRP3/Caspase-1/IL-1β Inflammasome
KPV prevents NLRP3 inflammasome complex assembly, reducing caspase-1 activation and the processing of pro-IL-1β and pro-IL-18 into their active inflammatory forms.
JAK/STAT Immune Regulation
KPV modulates JAK/STAT signaling in immune cells, reducing STAT1 and STAT3 phosphorylation in response to inflammatory stimuli while preserving STAT6 signaling (associated with anti-inflammatory M2 macrophage polarization).
Dosage Information
Calculation Results
Syringe Fill Level (100u syringe)
Protocols
No protocols featuring this peptide yet.
Browse All ProtocolsStability & Storage
KPV is supplied as a white lyophilized powder. Store at -20°C for long-term stability (24+ months) or 2-8°C for up to 12 months. As a small tripeptide (342 Da), KPV is inherently more stable than larger peptides.
Reconstitute with sterile or bacteriostatic water for injection use. For oral administration, KPV can be dissolved in water or encapsulated — its small size and PepT1-mediated absorption enable effective oral delivery. Store reconstituted solutions at 2-8°C and use within 28 days.
KPV has no cysteine or methionine residues, making it resistant to oxidative degradation. The proline residue provides moderate protease resistance. For oral use, enteric capsule formulations may enhance delivery to the intestinal epithelium where PepT1 is most highly expressed.
Side Effects & Precautions
Generally Well-Tolerated
KPV has demonstrated excellent tolerability in preclinical studies with no significant adverse effects reported at therapeutic doses.
No Immunosuppression
Despite potent anti-inflammatory activity, KPV does not cause general immunosuppression. It selectively reduces excessive inflammatory signaling while preserving normal immune surveillance and antimicrobial defense.
No Melanocortin Side Effects
Unlike full-length α-MSH, KPV does not activate melanocortin receptors and therefore does not cause skin darkening (hyperpigmentation), appetite suppression, or sexual arousal effects associated with melanocortin receptor activation.
Minimal Reported Adverse Effects
Injection site reactions (mild pain, redness) when administered subcutaneously. Oral administration has been well-tolerated in preclinical models.
Limited Human Safety Data
Comprehensive human clinical trial data is not yet available. Safety data is primarily derived from preclinical studies and extrapolated from the well-established safety profile of α-MSH and related melanocortin peptides.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Regulatory Status
KPV is not approved by the FDA or any major regulatory authority for clinical therapeutic use. It is classified as an investigational research compound and is available from peptide synthesis companies for laboratory research.
The peptide has not undergone formal clinical trials as a standalone therapeutic agent. Its parent compound α-MSH and related melanocortin analogs have extensive clinical investigation, providing context for KPV's potential therapeutic profile.
KPV is not on the WADA prohibited list and is not a scheduled or controlled substance in any jurisdiction.
Research Studies
The Anti-Inflammatory Tripeptide KPV Is Transported by PepT1
Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al.
Alpha-MSH(11-13) KPV Inhibits NF-κB in Intestinal Epithelial Cells
Kannengiesser K, Maaser C, Heidemann J, et al.
Oral Administration of KPV Attenuates Experimental Colitis
Laroui H, Dalmasso G, Nguyen HT, et al.
Alpha-Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry, Anti-inflammatory and Protective Effects
Brzoska T, Luger TA, Maaser C, et al.
NF-κB as a Target for Anti-Inflammatory Melanocortin Peptides
Manna SK, Aggarwal BB.
