2. Academic Validation
  3. Recent development of CDK inhibitors: An overview of CDK/inhibitor co-crystal structures

Recent development of CDK inhibitors: An overview of CDK/inhibitor co-crystal structures

  • Eur J Med Chem. 2019 Feb 15:164:615-639. doi: 10.1016/j.ejmech.2019.01.003.
Weiyan Cheng 1,  Zhiheng Yang 1,  Suhua Wang 1,  Ying Li 1,  Han Wei 1,  Xin Tian 2,  Quancheng Kan 3
Affiliations

Affiliations

  • 1 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.
  • 2 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. Electronic address: tianx@zzu.edu.cn.
  • 3 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. Electronic address: kanqc@zzu.edu.cn.
PMID: 30639897 DOI: 10.1016/j.ejmech.2019.01.003
Abstract

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.

Keywords

CDK; Co-crystal structure; Inhibitor; Pharmacological activity; Selectivity.

Figures