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
Institution
Title
MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.
Journal
Nature chemical biology
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
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 7:19
Last modification date
20/08/2019 16:02
Usage data
