LL-37 — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for LL-37, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| Bacterial membranes | Direct lytic activity | Concentration-dependent membrane permeabilisation with broad-spectrum activity |
| Formyl peptide receptor 2 (FPR2/ALX) | Agonist | Chemotactic activity for neutrophils, monocytes and T cells |
| Mammalian membranes | Cytotoxicity at higher concentration | The therapeutic window between antimicrobial and cytotoxic concentrations is narrow, which is the principal obstacle to systemic development |
§2.2Mechanism of action
LL-37 permeabilises bacterial membranes through an amphipathic helical mechanism and separately acts as a chemoattractant and immunomodulator through formyl peptide receptor 2. It also promotes angiogenesis and wound re-epithelialisation. Its narrow selectivity margin between antimicrobial and haemolytic activity has confined clinical development to topical and intralesional routes.[1,2]
§2.3Pharmacokinetics
No human pharmacokinetic characterisation of LL-37 has been identified. In the absence of a half-life, a volume of distribution and a clearance estimate, no dosing interval used in practice can be related to any exposure that produced an effect in any study, and the Institute records this as a first-order gap rather than a detail.
§2.4Interactions
- Anionic polymers, heparin and glycosaminoglycans bind and neutralise cationic peptides
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.