Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders
University of Science and Technology of China · Hefei National Center for Physical Sciences at Nanoscale · +6 more institutions
Abstract
The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of human diseases. A few compounds have been developed to inhibit NLRP3 inflammasome activation, but compounds directly and specifically targeting NLRP3 are still not available, so it is unclear whether NLRP3 itself can be targeted to prevent or treat diseases. Here we show that the compound CY-09 specifically blocks NLRP3 inflammasome activation. CY-09 directly binds to the ATP-binding motif of NLRP3 NACHT domain and inhibits NLRP3 ATPase activity, resulting in the suppression of NLRP3 inflammasome assembly and activation. Importantly, treatment with CY-09 shows remarkable therapeutic effects on mouse models of…
Citation impact
- FWCI
- 18.39
- Percentile
- 100%
- References
- 65
Authors
14- HJHua Jiang
University of Science and Technology of China, Hefei National Center for Physical Sciences at Nanoscale, Center for Excellence in Molecular Cell Science
- HHHongbin He
University of Science and Technology of China, Center for Excellence in Molecular Cell Science
- YCYun Chen
Xiamen University
- WHWei Huang
Xiamen University
- JCJinbo Cheng
University of Science and Technology of China, Center for Excellence in Molecular Cell Science
Topics & keywords
- Inflammasome
- In vivo
- Pathogenesis
- Gout
- Chemistry
- Pyrin domain
- Inflammation
- Medicine
- Good health and well-being
Funding
- NNNational Natural Science Foundation of ChinaAwards: 81330078, 81525013, 81722022, 81788104, 81422045, 81571609, U1405223
- CAChinese Academy of SciencesAwards: XDPB03, XDA12040310
- NKNational Key Research and Development Program of ChinaAwards: 2014CB910800, 2016YFA0502001
- FRFundamental Research Funds for the Central Universities