体内
药理学
神经炎症
巴基斯坦卢比
炎症
体外
化学
医学
糖酵解
生物化学
免疫学
生物
新陈代谢
生物技术
丙酮酸激酶
作者
Chenglong Gao,Gui‐Ge Hou,Jin Liu,Ru Tong,Yazhou Xu,Shunyi Zhao,Hui Ye,Luyong Zhang,Kaixian Chen,Yue‐Wei Guo,Tao Pang,Xu‐Wen Li
标识
DOI:10.1002/ange.201912489
摘要
Abstract Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti‐inflammation in LPS‐induced neuroinflammatory mice model and cerebral ischemic injury through anti‐neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti‐inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti‐neuroinflammatory effect in vitro and in vivo by inhibiting PKM2‐mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation‐related diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI