药效团
化学
细胞周期蛋白依赖激酶2
对接(动物)
立体化学
组合化学
IC50型
生长抑制
咪唑
体外
激酶
生物化学
蛋白激酶A
医学
护理部
作者
Yizhe Wu,Ying Huang,Lei Xu,Gang Cheng,Jing Chen,Yongzhou Hu,Daqiang Li,Xiaowu Dong
标识
DOI:10.1002/ardp.201700381
摘要
A novel series of imidazo[4,5-c]pyridine-based CDK2 inhibitors were designed from the structure of CYC202 via scaffold hopping strategy. These compounds were synthesized and biologically evaluated for their CDK2 inhibitory and in vitro anti-proliferation potential against cancer cell lines. Several compounds exhibited potent CDK2 inhibition with IC50 values of less than 1 µM. The most potent compound 5b showed excellent CDK2 inhibitory (IC50 = 21 nM) and in vitro anti-proliferation activity against three different cell lines (HL60, A549, and HCT116). The molecular docking and dynamic studies portrayed the potential binding mechanism between 5b and CDK2, and several key interactions between them were observed, which would be the reason for its potent CDK2 inhibitory and anti-proliferation activities. Therefore, the pyridin-3-ylmethyl moiety would serve as an excellent pharmacophore for the development of novel CDK2 inhibitors for targeted anti-cancer therapy.
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