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. Epub 2019 Jan 3.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / chemistry
  • Humans
  • Molecular Structure
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinases