Abstract
NLRP3 (NOD-like receptor pyrin domain-containing protein 3) is an innate immune sensor that contributes to the development of different diseases, including monogenic autoinflammatory syndromes, gout, atherosclerosis, and Alzheimer's disease. The molecule sulfonylurea MCC950 is a NLRP3 inflammasome inhibitor with potential clinical utility. However, the mechanism of action of MCC950 remains unknown. Here, we characterize the mechanism of action of MCC950 in both wild-type and autoinflammatory-related NLRP3 mutants, and demonstrate that MCC950 closes the 'open' conformation of active NLRP3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites / drug effects
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Furans
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HEK293 Cells
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology*
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Humans
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Indenes
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NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
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NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
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Protein Conformation
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Sulfonamides
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Sulfones / chemistry
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Sulfones / pharmacology*
Substances
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Furans
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Heterocyclic Compounds, 4 or More Rings
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Indenes
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Sulfonamides
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Sulfones
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N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide