MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
Nature chemical biology, 2019•nature.com
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.
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.
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.
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