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

Details

Serval ID
serval:BIB_DDFDF18FD7ED
Type
Article: article from journal or magazin.
Collection
Publications
Title
MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.
Journal
Nature chemical biology
Author(s)
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 AAB, Schroder K.
ISSN
1552-4469 (Electronic)
ISSN-L
1552-4450
Publication state
Published
Issued date
06/2019
Peer-reviewed
Oui
Volume
15
Number
6
Pages
556-559
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Adenosine Triphosphate/antagonists & inhibitors, Adenosine Triphosphate/metabolism, Binding Sites/drug effects, Heterocyclic Compounds, 4 or More Rings/chemistry, Heterocyclic Compounds, 4 or More Rings/pharmacology, Humans, Hydrolysis/drug effects, Inflammasomes/antagonists & inhibitors, Inflammasomes/biosynthesis, NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Sulfones/chemistry, Sulfones/pharmacology
Pubmed
Web of science
Create date
03/06/2019 8:19
Last modification date
20/08/2019 17:02
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