裂谷1
克里唑蒂尼
重新调整用途
坏死性下垂
药物重新定位
程序性细胞死亡
药理学
癌症研究
药品
医学
细胞凋亡
化学
生物
肿瘤科
生物化学
恶性胸腔积液
生态学
肺癌
作者
Yajie Yu,Min Li,Shufang Fu,Xiaoyan He,Xinqian Hu,Guo‐Qiang Zhu,Jia Wang,Xiaoling You,Yan Mou,Yang Liu,Jun Wei,Yunhong Zha
标识
DOI:10.1093/intimm/dxac061
摘要
Abstract Receptor-interacting protein kinase 1 (RIPK1) has emerged as a key regulator of cell death and inflammation, which are implicated in the pathogenesis of many inflammatory and degenerative diseases. RIPK1 is therefore a putative therapeutic target in many of these diseases. However, no pharmacological inhibitor of RIPK1-mediated cell death is currently in clinical use. Recognizing that a repurposed drug has an expedited clinical development pipeline, here we performed a high-throughput drug screen of Food and Drug Administration (FDA)-approved compounds and identified a novel use for crizotinib as an inhibitor of RIPK1-dependent cell death. Furthermore, crizotinib rescued TNF-α-induced death in mice with systemic inflammatory response syndrome. RIPK1 kinase activity was directly inhibited by crizotinib. These findings identify a new use for an established compound and are expected to accelerate drug development for RIPK1-spectrum disorders.
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