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  • Title: MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.
    Author: Coll RC, Hill JR, Day CJ, Zamoshnikova A, Boucher D, Massey NL, Chitty JL, Fraser JA, Jennings MP, Robertson AAB, Schroder K.
    Journal: Nat Chem Biol; 2019 Jun; 15(6):556-559. PubMed ID: 31086327.
    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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