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LL-37

Also known as: Cathelicidin C-Terminal Active Fragment, hCAP-18 Active Peptide

Research Only

Molecular Formula

C205 H340 N60 O53

Molecular Weight

4,493.33 Da

Half-Life

Unknown in human circulation (lacks in-vivo human PK studies; stability varies by matrix and formulation in vitro)

Sequence

LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES

Clinical Applications & Evidence

Mechanism of Action

In experimental models, LL-37 disrupts bacterial cell membranes via electrostatic interactions (carpet mechanism, oligomerization, and pore formation depending on lipid composition). It neutralizes bacterial lipopolysaccharides (LPS), acts as a chemoattractant via FPR2/ALX (formerly FPRL1) receptors, activates EGFR and MAPK pathways to promote epithelial cell migration and angiogenesis, and complexes with extracellular nucleic acids to modulate Toll-like receptor signaling.

Investigated Uses

  • Topical chronic wound healing (Investigational — Phase 1/2 venous leg ulcer & diabetic foot ulcer trials; mixed efficacy)
  • Antimicrobial & antibiofilm activity (Preclinical in-vitro & animal models)
  • Epithelial repair & angiogenesis (Preclinical cell & animal models)
Early Clinical / Animal Models

Regulatory & Safety Status

FDA Status

Research Only

WADA / Athletic Status

Not Explicitly Prohibited

Known Side Effects

Topical site irritation or mild burning (reported in topical clinical trials)Cytotoxicity to mammalian cells at elevated concentrations in vitro (≥13–25 μM)Systemic human adverse event dataset unavailable

Contraindications

  • WADA-tested athletes (Unapproved substance under S0 Non-Approved Substances)
  • Mechanistic uncertainty in psoriasis, rosacea, and systemic lupus (conditions associated with endogenous LL-37 overexpression)
  • Pregnancy and systemic administration (Unstudied; unknown safety profile)

Drug Interactions

  • Antibiotics (In-vitro co-incubation studies report synergistic bacterial inhibition with select agents)
  • Immunosuppressive therapies (Theoretical immunomodulatory overlap; clinical interactions unstudied)

Citations & Clinical Trials

DiVA Portal Topical LL-37 in Venous Leg Ulcer Healing: Randomized Phase 1/2 Trial PubMed Central Multicenter Phase 2b Trial of LL-37 in Hard-to-Heal Venous Leg Ulcers (2022) PubMed Efficacy of LL-37 Cream on Diabetic Foot Ulcer Healing (2023) PubMed Wound Healing Activity of Human Antimicrobial Peptide LL-37 (2011)