Cathelicidin (hCAP-18 / Synthetic Derivatives)vsLL-37

Molecular Formula

hCAP-₁₈: ~₁₈ kDa precursor protein (₁₇₀ AA); SAAP-₁₄₈: C₁₅₅H₂₅₃N₄₉O₃₁ (approximate), MW ₃,₂₆₇.₁ Da

Molecular Weight

hCAP-18 precursor: ~18,000 Da; SAAP-148: 3,267.1 Da; OP-145: ~2,900 Da

Half-Life

Plasma half-life: minutes (proteolytic degradation); local tissue persistence: hours at therapeutic concentrations in wound environment; enhanced stability compared to LL-37 due to N-terminal acetylation and C-terminal amidation

Bioavailability

Topical bioavailability optimized in hypromellose ointment formulations; SAAP-148 retains activity in human plasma unlike LL-37; systemic bioavailability limited by proteolytic degradation

CAS Number

Not assigned (SAAP-148 and OP-145 are novel synthetic derivatives)

Molecular Formula

C₂₀₅H₃₄₀N₆₀O₅₃

Molecular Weight

4,493.26 Da

Half-Life

Short systemic half-life (minutes) due to protease susceptibility; local tissue persistence at wound sites is longer due to binding to extracellular matrix components and lipid membranes

Bioavailability

Topical application achieves high local wound-bed concentrations; systemic bioavailability limited by rapid proteolytic degradation and serum protein binding; not intended for oral delivery

CAS Number

154947-66-7

Common

• Local application site irritation
• Local inflammatory response
• Mild wound exudate increase

Uncommon

• Localized urticaria
• Transient pain at injection site

Serious

• Hemolytic activity at supratherapeutic doses

Common

• Local site irritation
• Transient stinging or burning
• Mild perilesional erythema
• Increased wound exudate

Uncommon

• Allergic contact reaction

Serious

• Hemolytic activity at systemic concentrations

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

Cathelicidin peptides (natural and synthetic) are not FDA-approved and have no completed human clinical trials. Animal studies demonstrate broad-spectrum antimicrobial activity without systemic toxicity at therapeutic concentrations. However, concern exists regarding immunological tolerance—cathelicidin derivatives can trigger innate immune activation and inflammatory responses at high concentrations. The peptide's mechanism on immune cells is incompletely understood in humans, and effects on chronic immune signaling, tolerance development, or off-target immune activation remain uncharacterized. Bacterial resistance development to cathelicidin-based therapeutics is theoretically possible but not yet documented clinically.

Contraindications

• xKnown hypersensitivity to cathelicidin-derived peptides or formulation components
• xPregnancy and breastfeeding — insufficient reproductive safety data for synthetic derivatives
• xActive autoimmune conditions involving cathelicidin dysregulation (e.g., rosacea, psoriasis) — exogenous cathelicidin peptides may exacerbate inflammation
• xSevere systemic immunodeficiency without medical supervision — immune modulation effects may be unpredictable

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

LL-37 is an endogenous cathelicidin antimicrobial peptide naturally produced by immune cells and epithelial tissues, conferring inherent biocompatibility and low toxicity at physiological concentrations. Synthetic LL-37 shows excellent safety in in vitro immune assays and animal models with no hepatotoxicity, nephrotoxicity, or genotoxicity at relevant doses. At elevated concentrations, the cationic amphipathic structure can cause hemolysis and cell membrane damage, but therapeutic doses are far below these thresholds. Injection site reactions are minimal in research applications.

Contraindications

• xKnown hypersensitivity to cathelicidin peptides or formulation components
• xActive hemolytic conditions — LL-37 demonstrates concentration-dependent hemolytic activity
• xPregnancy and breastfeeding — insufficient reproductive safety data from clinical trials
• xSevere renal impairment — peptide clearance may be altered