药效团
限制点
细胞周期蛋白依赖激酶2
细胞周期进展
细胞周期
细胞周期蛋白依赖激酶
计算生物学
激酶
细胞周期蛋白依赖激酶4
化学
生物
蛋白激酶A
生物化学
细胞
作者
Pingping Chen,Yurui Xu,Xuanyi Li,Hequan Yao,Kejiang Lin
出处
期刊:Future Medicinal Chemistry
[Newlands Press Ltd]
日期:2020-01-01
卷期号:12 (2): 127-145
被引量:8
标识
DOI:10.4155/fmc-2019-0062
摘要
Aim: CDK4/6 have critical roles in the early stage of the cell cycle. CDK2 acts later in the cell cycle and has a considerably broader range of protein substrates, some of which are essential for normal cell proliferation. Therefore, increasing the selectivity of cyclin-dependent kinase (CDK) inhibitors is critical. Methodology: In this study, we construct a versatile, specific CDK4 pharmacophore model that not only matches well with 8119 of the reported 9349 CDK4/6 inhibitors but also differentiates from the CDK2 pharmacophore. Results & Conclusion: we demonstrate the activity and selectivity determinants of CDK4/6 selective inhibitors based on the CDK4 pharmacophore model. Finally, we propose the future optimization strategy for CDK4/6 selective inhibitors, providing a theoretical basis for further research and development of CDK4/6 selective inhibitors.
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