Guan Haixing, Du Yongli, Han Weiwei, Shen Jingkang, Li Qunyi
School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
Anticancer Agents Med Chem. 2017;17(5):646-657. doi: 10.2174/1871520617666170103095527.
Cyclin-Dependent Kinases 4 (CDK4) belongs to a family of serine-threonine protein kinase and plays key regulatory role in G1-phase of cell cycle progression. Compelling evidences have shown that targeting CDK4 pathway is an attractive proposition for tumor therapy. Recent progresses of selective small molecule CDK4 inhibitors in cancer therapy have endorsed the field to be interested and attractive. In this review, we will discuss the recent developments of CDK4 inhibitors on several aspects such as the structure of CDK4, the working mechanism of CDK4 inhibitors, the structure activity relationships (SARs) of the selective CDK4 inhibitors and the latest developments of the selective CDK4 inhibitors in clinical trials.
细胞周期蛋白依赖性激酶4（CDK4）属于丝氨酸-苏氨酸蛋白激酶家族，在细胞周期进程的G1期发挥关键调节作用。有力证据表明，靶向CDK4通路是肿瘤治疗的一个有吸引力的策略。选择性小分子CDK4抑制剂在癌症治疗中的最新进展使该领域备受关注且颇具吸引力。在本综述中，我们将从几个方面讨论CDK4抑制剂的最新进展，如CDK4的结构、CDK4抑制剂的作用机制、选择性CDK4抑制剂的构效关系（SARs）以及选择性CDK4抑制剂在临床试验中的最新进展。
