Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders

• DOI: 10.1084/jem.20171419
• Publication Date: 2017-10-11T14:40:09Z
• Authors: Hua Jiang; Hongbin He; Yun Chen; Wei Huang; Jinbo Cheng; Jin Ye; Aoli Wang; Jinhui Tao; Chao Wang; Qingsong Liu; Tengchuan Jin; Wei Jiang; Xianming Deng; Rongbin Zhou
• Keywords: Pathogenesis; Pyrin domain

The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety human diseases. A few compounds have developed to inhibit activation, but directly and specifically targeting are still not available, so it is unclear whether itself can be targeted prevent or treat Here we show that compound CY-09 blocks activation. binds ATP-binding motif NACHT domain inhibits ATPase activity, resulting suppression assembly Importantly, treatment with shows remarkable therapeutic effects on mouse models cryopyrin-associated autoinflammatory syndrome (CAPS) type 2 diabetes. Furthermore, active ex vivo for monocytes from healthy individuals synovial fluid cells patients gout. Thus, our results provide selective direct small-molecule inhibitor indicate combat NLRP3-driven