By the same authors

From the same journal

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

Research output: Contribution to journalArticlepeer-review

Author(s)

  • 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

Department/unit(s)

Publication details

JournalNATURE CHEMICAL BIOLOGY
DateAccepted/In press - 22 Mar 2019
DateE-pub ahead of print - 13 May 2019
DatePublished (current) - Jun 2019
Issue number6
Volume15
Number of pages4
Pages (from-to)556-559
Early online date13/05/19
Original languageEnglish

Abstract

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.

    Research areas

  • 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

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations