Recent advances in the treatment of gout with NLRP3 inflammasome inhibitors

Bioorg Med Chem. 2024 Oct 1:112:117874. doi: 10.1016/j.bmc.2024.117874. Epub 2024 Aug 16.

Abstract

Gout is an autoinflammatory disorder characterized by the accumulation of monosodium urate crystals in joints and other tissues, representing the predominant type of inflammatory arthritis with a notable prevalence and propensity for severe outcomes. The NLRP3 inflammasome, a member of the pyrin domain-containing NOD-like receptor family, exerts a substantial impact on both innate and adaptive immune responses and serves as a pivotal factor in the pathogenesis of gout. In recent years, there has been significant academic and industrial interest in the development of NLRP3-targeted small molecule inhibitors as a promising therapeutic approach for gout. To assess the advancements in NLRP3 inflammasome inhibitors for gout treatment, this review offers a comprehensive analysis and evaluation of current clinical candidates and other inhibitors targeting NLRP3 inflammasome from a chemical structure standpoint, with the goal of identifying more efficacious options for clinical management of gout.

Keywords: Drug discovery; Gout; Inflammatory arthritis; NLRP3 inflammasome inhibitors; Uric acid.

Publication types

  • Review

MeSH terms

  • Animals
  • Gout* / drug therapy
  • Humans
  • Inflammasomes* / antagonists & inhibitors
  • Inflammasomes* / metabolism
  • Molecular Structure
  • NLR Family, Pyrin Domain-Containing 3 Protein* / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism

Substances

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