Therapeutic potential of MCC950, a specific inhibitor of NLRP3 inflammasome

Eur J Pharmacol. 2022 Aug 5:928:175091. doi: 10.1016/j.ejphar.2022.175091. Epub 2022 Jun 14.

Abstract

NOD-like receptor protein 3 (NLRP3), an important intracellular pattern recognition receptor, is a component of the NLRP3 inflammasome along with apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and pro-caspase-1. Previous studies have shown that dysregulation of NLRP3 inflammasome may be associated with several human diseases, and therefore blocking NLRP3 inflammasome activation may represent a therapeutic strategy for various diseases. MCC950 is a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. In recent years, research on MCC950 has expanded; its targets are gradually being elucidated, and its metabolism and toxicity have been a focus of study. Preclinical research of MCC950 has yielded promising findings, and MCC950 has shown good efficacy in the treatment of autoimmune diseases, cardiovascular diseases, metabolic diseases and other diseases. Furthermore, clinical trials of MCC950 and other inhibitors of NLRP3 inflammasome have also been conducted. In this review, we discuss the drug targets, metabolism, toxicity and preclinical and clinical research advances of MCC950. We further discuss the clinical therapeutic potential of MCC950 to provide insights for the further study and application of MCC950.

Keywords: Drug targets; MCC950; Metabolism; NLRP3 inflammasome; Preclinical researches; Toxicity.

Publication types

  • Review

MeSH terms

  • Furans / pharmacology
  • Furans / therapeutic use
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Indenes
  • Inflammasomes* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • NLR Proteins
  • Sulfonamides
  • Sulfones / pharmacology

Substances

  • Furans
  • Heterocyclic Compounds, 4 or More Rings
  • Indenes
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLR Proteins
  • Sulfonamides
  • Sulfones
  • N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide