Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Eur J Med Chem. 2019 Feb 15;164:615-639. doi: 10.1016/j.ejmech.2019.01.003. Epub 2019 Jan 3.
The cyclin-dependent protein kinases (CDKs) are protein-serine/threonine kinases that display crucial effects in regulation of cell cycle and transcription. While the excessive expression of CDKs is intimate related to the development of diseases including cancers, which provides opportunities for disease treatment. A large number of small molecules are explored targeting CDKs. CDK/inhibitor co-crystal structures play an important role during the exploration of inhibitors. So far nine kinds of CDK/inhibitor co-crystals have been determined, they account for the highest proportion among the Protein Data Bank (PDB) deposited crystal structures. Herein, we review main co-crystals of CDKs in complex with corresponding inhibitors reported in recent years, focusing our attention on the binding models and the pharmacological activities of inhibitors.
细胞周期蛋白依赖性蛋白激酶（CDKs）是一类丝氨酸/苏氨酸蛋白激酶，在细胞周期和转录调控中发挥着关键作用。虽然 CDK 的过度表达与包括癌症在内的多种疾病的发生密切相关，为疾病治疗提供了机会。目前已经探索了大量针对 CDK 的小分子。CDK/抑制剂共晶结构在抑制剂的探索中起着重要作用。迄今为止，已经确定了 9 种 CDK/抑制剂共晶结构，它们在蛋白质数据库（PDB）中所占比例最高。本文综述了近年来报道的 CDK 与相应抑制剂的主要共晶，重点关注抑制剂的结合模式和药理学活性。
