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For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement.
AMIRAVOResearch Library

KPV vs LL-37

KPV and LL-37 are both naturally occurring peptides studied for anti-inflammatory and antimicrobial activity, but they differ greatly in size, origin and clinical testing 4,7. KPV is the C-terminal tripeptide (Lys-Pro-Val, residues 11-13) of alpha-melanocyte-stimulating hormone and has been studied only in cells and animals 1,6. LL-37 is the 37-amino-acid antimicrobial peptide released from hCAP-18, the product of the only human cathelicidin gene, and has reached phase 2b trials as a topical wound treatment 7,9. Neither is FDA-approved, and the FDA lists both among bulk substances for compounding that may present significant safety risks, as of 22 April 2026 13.

Unbranded reference vial illustrating KPV; not an actual product
KPV
Not approved — research use only
Unbranded reference vial illustrating LL-37; not an actual product
LL-37
Not approved — research use only

Side by side

FieldKPVLL-37
ClassMelanocortin-derived tripeptide, alpha-MSH(11-13) 1Human cathelicidin antimicrobial peptide 7,8
Origin and structureLys-Pro-Val, the carboxy-terminal three residues of alpha-MSH (SYSMEHFRWGKPV) 437-amino-acid C-terminal peptide cleaved by proteinase 3 from hCAP-18, stored in neutrophil granules and expressed by keratinocytes and epithelial cells 7,12
Proposed mechanismIn cells, taken up by the PepT1 transporter and inhibits NF-kappaB and MAP kinase signalling 2; in mice, effects appear at least partly independent of melanocortin receptors 1,3Broad-spectrum antimicrobial with chemotactic and immunomodulatory activity; chemotaxis via formyl peptide receptor-like 1 7,8
Half-lifeNot located in the sources reviewedNot located in the sources reviewed
Highest human trial phaseNo registered trials located on ClinicalTrials.gov (searched 24 October 2026) 6Phase 2b (topical, venous leg ulcers, 148 patients) 9
FDA statusNot FDA-approved; listed among bulk substances that may present significant safety risks (nomination withdrawn), as of 22 April 2026 13Not FDA-approved; listed as cathelicidin LL-37 among bulk substances that may present significant safety risks (nomination withdrawn), as of 22 April 2026 13
Published human outcomesNone located; human data are limited to cell lines 2,6In the phase 2b leg-ulcer trial, healing did not differ from placebo in the full population 9; a diabetic foot ulcer trial reported a larger increase in granulation index 10
Safety signalsFDA has not identified any human exposure data for KPV by any route 13FDA cites nonclinical findings of detrimental effects on male reproduction and possible protumorigenic effects 13; skin lesions were reported in a melanoma patient receiving intratumoral LL-37 12
WADA statusNot named on the 2026 List; S0 covers unapproved pharmacological substances not addressed elsewhere 14Not named on the 2026 List; S0 covers unapproved pharmacological substances not addressed elsewhere 14
Who funded the evidenceAcademic groups; mechanistic colitis work was supported by US NIH (NIDDK) grants 2,5The phase 2b leg-ulcer trial was run by developer Promore Pharma AB, which develops LL-37 as ropocamptide 9; the foot-ulcer trial was funded by Universitas Indonesia 10

KPV: what the data says

KPV research is preclinical. In two mouse models of colitis (animal data), KPV-treated mice showed reduced inflammatory infiltrates and colonic myeloperoxidase activity, including in mice lacking a functional melanocortin-1 receptor 1. In human intestinal epithelial and T-cell lines (cell data), KPV entered cells via the PepT1 transporter and reduced NF-kappaB and MAP kinase signalling and pro-inflammatory cytokine secretion 2.

  • In a mouse peritonitis model (animal data), KPV reduced leukocyte accumulation without raising cAMP, and the authors concluded it was unlikely to act through melanocortin receptors 3.
  • In vitro, alpha-MSH peptides including KPV inhibited Staphylococcus aureus and Candida albicans (cell-free and cell data) 4.
  • Formulation work has tested KPV in hyaluronic-acid nanoparticles in a mouse colitis model (animal data) 5. No human trials were located 6.

LL-37: what the data says

LL-37 is part of the human innate immune system: it is liberated from hCAP-18 during neutrophil degranulation and is also produced by keratinocytes and epithelial cells 7. Reviews describe broad-spectrum antimicrobial, chemotactic and immunomodulatory activity in cell and animal studies 8.

  • In the 148-patient phase 2b HEAL LL-37 trial (humans), there was no significant difference in healing versus placebo in the full population; a post hoc subgroup with large wounds differed 9.
  • In a randomized diabetic foot ulcer trial in Indonesia (humans), the granulation index rose more with LL-37 cream, while inflammatory cytokines and bacterial counts did not differ significantly 10.
  • A phase 1/2 study of intratumoral LL-37 in melanoma enrolled 4 participants 11.

Key research differences

  • Size and source: KPV is a three-residue fragment of alpha-MSH 4, whereas LL-37 is a 37-residue peptide cleaved from the cathelicidin precursor hCAP-18 7.
  • Human evidence: no human trials of KPV were located 6, while LL-37 has randomized topical trials up to phase 2b 9.
  • Mechanism: KPV's anti-inflammatory activity in cells is linked to PepT1 uptake and NF-kappaB inhibition 2; LL-37 acts as a membrane-active antimicrobial and chemotactic signal via formyl peptide receptor-like 1 7.
  • FDA concerns: for KPV the FDA notes no human exposure data at all, whereas for LL-37 it cites nonclinical reproductive and protumorigenic findings 13.

Where the evidence is limited

No study has compared KPV and LL-37 directly. KPV data come almost entirely from mouse colitis and peritonitis models and cell lines 1,2,3, while LL-37 data include topical human wound trials whose primary results were mixed 9,10. The two peptides were studied for different conditions and routes, and no human pharmacokinetic data were located for either 6,9. The largest LL-37 trial was conducted by the company developing it 9.

Frequently asked questions

Is KPV part of alpha-MSH?
Yes. KPV is alpha-MSH(11-13), the carboxy-terminal tripeptide of the 13-residue hormone 1,4. Mouse data suggest its anti-inflammatory effect may not depend on melanocortin receptors 3.
Has LL-37 been tested in humans?
Yes, as a topical treatment for chronic wounds. A 148-patient phase 2b trial in venous leg ulcers found no significant difference from placebo in the full population 9.
Can KPV and LL-37 be compared directly?
No. No head-to-head study was located, and KPV has no human trials while LL-37 has been studied mainly as a topical wound treatment 6,9.
What does the FDA say about KPV and LL-37?
Both appear on the FDA's page of bulk substances that may present significant safety risks; the FDA notes no human exposure data for KPV and nonclinical reproductive and protumorigenic findings for LL-37 13.

References

  1. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease Inflammatory Bowel Diseases. 2008
  2. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation Gastroenterology. 2008
  3. 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
  4. Antimicrobial effects of alpha-MSH peptides Journal of Leukocyte Biology. 2000
  5. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis Molecular Therapy. 2017
  6. ClinicalTrials.gov API search for KPV (0 studies returned, 24 October 2026) ClinicalTrials.gov. 2026
  7. Cathelicidins: a family of endogenous antimicrobial peptides Current Opinion in Hematology. 2002
  8. LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity Pharmacological Reports. 2016
  9. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial Wound Repair and Regeneration. 2021
  10. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial Archives of Dermatological Research. 2023
  11. Intratumoral Injections of LL37 for Melanoma (NCT02225366) ClinicalTrials.gov. 2021
  12. Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features Journal of Cutaneous Pathology. 2018
  13. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026) FDA (Human Drug Compounding). 2026
  14. Prohibited List 2026 (in force 1 January 2026) World Anti-Doping Agency. 2026

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.