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


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.

Type Journal
ISBN 1552-4450
Authors Coll, R. C.; Hill, J. R.; Day, C. J.; Zamoshnikova, A.; Boucher, D.; Massey, N. L.; Chitty, J. L.; Fraser, J. A.; Jennings, M. P.; Robertson, A. A. B.; Schroder, K.
Responsible Garvan Author Jessica Chitty
Publisher Name Nature Chemical Biology
Published Date 2019-06-01
Published Volume 15
Published Issue 6
Published Pages 556-559
Status Published in-print
DOI 10.1038/s41589-019-0277-7
URL link to publisher's version