Recent progress of cyclin-dependent kinase inhibitors as potential anticancer agents

被引:9
作者
Li, Tinghan [1 ,2 ]
Weng, Tianwei [1 ,2 ]
Zuo, Minzan [1 ,2 ]
Wei, Zhihui [1 ,2 ]
Chen, Ming [1 ,2 ]
Li, Zhiyu [1 ,2 ]
机构
[1] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
[2] China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Nanjing 210009, Peoples R China
关键词
cancer therapy; cell cycle; clinical trials; cyclin-dependent kinases; small-molecule inhibitors; structure-activity relationships; X-RAY CRYSTALLOGRAPHY; DINACICLIB SCH 727965; I DOSE-ESCALATION; CDK INHIBITORS; BREAST-CANCER; CELL-CYCLE; P-TEFB; SELECTIVE INHIBITOR; BIOLOGICAL EVALUATION; MULTIPLE-MYELOMA;
D O I
10.4155/fmc-2016-0129
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Deregulation of the cell cycle is a common feature in human cancer. The inhibition of cyclin-dependent kinases (CDKs), which play a crucial role in control of the cell cycle, has always been one of the most promising areas in cancer chemotherapy. This review first summarizes the biology of CDKs and then focuses on the recent advances in both broad-range and selective CDK inhibitors during the last 5 years. The design rationale, structural optimization and structure-activity relationships analysis of these small molecules have been discussed in detail and the key interactions with the amino-acid residues of the most important compounds are highlighted. Future perspectives for CDKs inhibitors will be defined in the development of highly selective CDK inhibitors, an accurate knowledge of gene control mechanism and further predictive biomarker research.
引用
收藏
页码:2047 / 2076
页数:30
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