MCC950 in the treatment of NLRP3-mediated inflammatory diseases: Latest evidence and therapeutic outcomes

Int Immunopharmacol. 2022 May:106:108595. doi: 10.1016/j.intimp.2022.108595. Epub 2022 Feb 3.

Abstract

Evidence suggests that various innate immune system components are involved in pathological inflammatory conditions. Among these components, the NLR family pyrin domain containing 3 (NLRP3) as an inflammasome can participate in destructive inflammatory responses by inducing the production of the active form of inflammatory cytokines. The NLRP3 could be involved in the pathogenesis of several inflammatory and autoimmune diseases such as type 2 diabetes mellitus, multiple sclerosis (MS), atherosclerosis, Alzheimer's disease (AD), cryopyrin-associated periodic syndrome (CAPS), and infectious diseases. Therefore, the inhibition of NLRP3 can be a useful treatment option for inflammatory diseases. In this regard, MCC950, as a small molecule, is capable of inhibiting NLRP3 and, following inhibition of NLRP3, production of interleukin-1β (IL-1β) and IL-18 as pro-inflammatory cytokines reduced. Interestingly, the MCC950 can inhibit NLRP3 but no other inflammasomes such as NLRP1 and NLR family CARD domain containing 4 (NLRC4). This review summarized the structure and mechanism of action of MCC950 in the control of NLRP3-dependent inflammation and the role of MCC950 in the treatment of NLRP3-mediated inflammatory diseases based on the latest studies.

Keywords: Inflammasome; Inflammation; MCC950; NLRP3.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / drug therapy
  • Disease Models, Animal
  • Furans / therapeutic use
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Indenes
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein* / physiology
  • Sulfonamides
  • Sulfones / pharmacology
  • Treatment Outcome

Substances

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