化学
细胞周期蛋白依赖激酶7
二价(发动机)
分子
细胞周期蛋白依赖激酶
激酶
立体化学
生物化学
生物物理学
有机化学
蛋白激酶A
细胞周期蛋白依赖激酶2
细胞周期
细胞凋亡
金属
生物
作者
Wenzhi Ji,Guangyan Du,Jie Jiang,Wenchao Lu,Caitlin E. Mills,Linjie Yuan,Fen Jiang,Zhixiang He,Gary A. Bradshaw,Mirra Chung,Zixuan Jiang,Woong Sub Byun,Stephen M. Hinshaw,Tinghu Zhang,Nathanael S. Gray
标识
DOI:10.1016/j.ejmech.2024.116613
摘要
Cyclin-dependent kinase 7, along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs cell cycle progression via T-loop phosphorylation of cell cycle CDKs. Pharmacological inhibition of CDK7 leads to selective anti-cancer effects in cellular and in vivo models, motivating several ongoing clinical investigations of this target. Current CDK7 inhibitors are either reversible or covalent inhibitors of its catalytic activity. We hypothesized that small molecule targeted protein degradation (TPD) might result in differentiated pharmacology due to the loss of scaffolding functions. Here, we report the design and characterization of a potent CDK7 degrader that is comprised of an ATP-competitive CDK7 binder linked to a CRL2
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