Cdk5——肿瘤新靶点及其抑制剂研究进展

Progress in the study of new cancer target Cdk5 and its inhibitors

细胞周期蛋白依赖性激酶-5(cyclin-dependent kinase-5,Cdk5)是一类丝氨酸/苏氨酸蛋白激酶,参与神经细胞生长发育和信号传导调控。Cdk5的过表达与肿瘤的发生、发展和凋亡有着密切关系。Cdk5抑制剂的研究正成为癌症治疗的热门领域。本文介绍了Cdk5的生物学功能和作用机制,重点阐述以ATP为锚点的小分子抑制剂和介导蛋白-蛋白相互作用的多肽等抑制剂的最新进展。

Cyclin-dependent kinase-5（Cdk5） is a kind of Ser/Thr kinases in the signaling pathway, which regulates the neural development. The recent studies have confirmed that hyperactivation of Cdk5 is closely associated with the evolution, progression and apoptosis of tumors. The Cdk5 inhibitors have been extensively studied in the drug discovery against cancer. The structure features of these inhibitors and molecular mechanisms of their activities have provided clues for the drug development. In the second generation Cdk5 inhibitors, the ATP-binding pocket, a highly conserved site, has been targeted in the drug design in most cases. In addition, a growing number of peptides has been generated by targeting the protein/protein interfaces of Cdk5.