酪蛋白激酶2
蛋白质水解
化学
蛋白酶体
磷酸化
泛素
蛋白质降解
蛋白激酶A
激酶
细胞生物学
苏氨酸
生物化学
蛋白激酶B
泛素连接酶
丝氨酸
细胞周期蛋白依赖激酶2
生物
酶
基因
作者
Hong Chen,Feihong Chen,Nannan Liu,Xinyi Wang,Shaohua Gou
标识
DOI:10.1016/j.bioorg.2018.09.005
摘要
As a ubiquitous, highly pleiotropic and constitutively active serine/threonine protein kinase, casein kinase 2 (CK2) is closely associated with tumorigenesis by its overexpression in cancer cells. Here we report several proteolysis targeting chimeras (PROTACs) via "click reaction" to connect a CK2 inhibitor (CX-4945) and pomalidomide for degradation of CK2 protein. Among them, compound 2 degraded CK2 in a dose and time-dependent manner, and kept CK2 at a low basal level by recruiting ubiquitin-proteasome system. The degradation of CK2 resulted in the reduced phosphorylation of Akt and the up-regulation of p53. As a CK2 protein degrader, 2 showed the analogous cytotoxicity to CX-4945 but with a quite different mechanism of action from the CK2 inhibitor, hinting that degradation of CK2 proteins by PROTACs is a potential way for cancer treatments.
科研通智能强力驱动
Strongly Powered by AbleSci AI