MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

Rebecca C Coll, James R Hill, Christopher J Day, Alina Zamoshnikova, Dave Boucher, Nicholas L Massey, Jessica L Chitty, James A Fraser, Michael P Jennings, Avril A B Robertson, Kate Schroder

Research output: Contribution to journalArticlepeer-review


Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and specific small-molecule inhibitor of the NLRP3 pathway, but its molecular target is not defined. Here, we show that MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, thereby blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation.

Original languageEnglish
Pages (from-to)556-559
Number of pages4
Issue number6
Early online date13 May 2019
Publication statusPublished - Jun 2019


  • Adenosine Triphosphate/antagonists & inhibitors
  • Binding Sites/drug effects
  • Heterocyclic Compounds, 4 or More Rings/chemistry
  • Humans
  • Hydrolysis/drug effects
  • Inflammasomes/antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors
  • Sulfones/chemistry

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