Development of small molecule inhibitors targeting NLRP3 inflammasome pathway for inflammatory diseases

Eur J Med Chem. 2020 Jan 1:185:111822. doi: 10.1016/j.ejmech.2019.111822. Epub 2019 Oct 30.

Abstract

NLRP3 (Nod-like receptor protein 3) belongs to the NOD-like receptor family, which is activated by pathogen and damage-associated signals to form a multimeric protein complex, known as the NLRP3 inflammasome. NLRP3 inflammasome activation leads to release of proinflammatory cytokines IL-1β and IL-18, thus inducing pyroptosis, a programmed cell death mechanism. Dysregulation of the NLRP3 inflammasome pathway is closely related to the development of many human diseases, such as neuroinflammation, metabolic inflammation, and immune inflammation. Emerging studies have suggested NLRP3 inflammasome as a potential drug-target for inflammatory diseases. Several small molecules have recently been identified to target the NLRP3 inflammasome pathway directly or indirectly and alleviate related disease pathology. This review summarizes recent evolving landscape of small molecule inhibitor development targeting the NLRP3 inflammasome pathway.

Keywords: Anti-inflammatory; Inhibitors; NLRP3 inflammasome; Pyroptosis; Structure-activity relationship.

Publication types

  • Review

MeSH terms

  • Humans
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Molecular Structure
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Small Molecule Libraries