CGRP vs LL-37

Binds CLR/RAMP1 receptor complex. Causes vasodilation via cAMP/PKA/nitric oxide pathway. Modulates nociceptive signaling in the trigeminal system. Promotes bone healing and has anti-inflammatory effects in peripheral tissues.

CGRP (calcitonin gene-related peptide) is a 37-amino-acid endogenous neuropeptide produced by alternative splicing of the calcitonin gene, expressed predominantly in sensory neurons of the trigeminal system and peripheral vasculature, where it functions as a potent vasodilator and pain neuromodulator central to migraine pathophysiology. CGRP activates its receptor complex (CLR/RAMP1) to mediate vasodilation and nociceptive signal amplification; during migraine attacks, trigeminal activation releases CGRP at elevated plasma concentrations, and blockade of this pathway has been established as the primary validated pharmacological target for modern preventive migraine therapy. Phase 3 randomized controlled trials published in the New England Journal of Medicine and the Lancet — including the STRIVE trial (Goadsby et al. 2017) and a Phase 3b study in treatment-refractory patients — demonstrated that anti-CGRP monoclonal antibodies significantly reduced monthly migraine days versus placebo, validating the pathway and supporting FDA approval of erenumab, fremanezumab, and galcanezumab. CGRP itself is an endogenous neuropeptide and is not a therapeutic agent that is compounded or administered by providers; the FDA-approved interventions are monoclonal antibody and small-molecule receptor antagonists available by prescription, and exogenous CGRP peptide is exclusively a research tool compound used in vasodilatory and pain signaling pharmacology studies.

Human cathelicidin antimicrobial peptide; disrupts bacterial membranes and modulates innate immune response via TLR signaling

LL-37 is the mature human cathelicidin antimicrobial peptide, a 37-amino-acid cationic peptide generated by proteolytic cleavage of the hCAP18 precursor protein, constitutively expressed in neutrophil granules and inducibly expressed in keratinocytes and epithelial cells of the skin, lung, and gastrointestinal tract as a component of innate antimicrobial defense. LL-37 disrupts bacterial and fungal membranes through electrostatic interaction with anionic lipopolysaccharide and membrane phospholipids, and also modulates inflammatory responses through formyl peptide receptor 2 (FPR2/ALX) activation, promotes wound healing via EGFR transactivation, and contributes to neutrophil extracellular trap formation and antiviral defense. Human studies have documented LL-37 expression in the context of severe soft tissue infections caused by Streptococcus pyogenes, and biochemical characterization of the hCAP18/LL-37 prosequence has identified antimicrobial and protease-inhibitory functions relevant to human skin defense biology. LL-37 is a research compound with no FDA approval for any indication; exogenous synthetic LL-37 administration is investigational with no completed human clinical trials establishing safety or efficacy for wound healing, antimicrobial, or immunomodulatory applications. LL-37 dosage and administration: No human clinical trial has established a dosage protocol for exogenous LL-37. Preclinical and in vitro studies have used LL-37 at concentrations ranging from 1–50 µg/mL in cellular models. Animal models have employed weight-based dosing via subcutaneous or intravenous delivery. Topical formulations for wound healing and antimicrobial applications have been investigated at varying concentrations, with interest in hydrogel delivery systems for sustained local release. LL-37 is rapidly degraded by host proteases in vivo, which limits systemic bioavailability following subcutaneous injection; this degradation susceptibility has driven research into protease-resistant LL-37 analogues and encapsulated formulations. LL-37 is a research compound with no approved human dosing guidelines for any indication.