化学
蛋白质水解
体内
前药
细胞周期蛋白依赖激酶
激酶
生物利用度
药理学
癌症研究
生物化学
细胞凋亡
细胞周期
酶
生物
生物技术
作者
Mingming Wei,Rui Zhao,Yuting Cao,Wei Yue,Ming Li,Zhiqiang Dong,Yulin Liu,Hao Ruan,Ying Li,Sheng Cao,Zhixiang Tang,Yuanyuan Zhou,Wei Song,Yubo Wang,Jiefu Wang,Guang Yang,Cheng Yang
标识
DOI:10.1016/j.ejmech.2020.112903
摘要
A growing number of reports suggested that the inhibitor targeting cyclin-dependent kinases (CDK) 2/4/6 can act as a more feasible chemotherapy strategy. In the present paper, a novel PROTAC molecule was developed based on the structure of Ribociclib's derivative. In malignant melanoma cells, the degrader can not only degrade CDK 2/4/6 simultaneously and effectively, but also remarkably induce cell cycle arrest and apoptosis of melanoma cells. Moreover, PROTAC molecules with CRBN ligands always have poor oral bioavailability. We developed the orally bioavailable prodrug for the first time. It would provide general solution for oral administration of the PROTAC molecules, derived from CRBN ligands, for animal test conveniently.
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