Binding patterns and structure-activity relationship of CDK8 inhibitors

Bioorg Chem. 2020 Mar:96:103624. doi: 10.1016/j.bioorg.2020.103624. Epub 2020 Jan 25.

Abstract

A major goal of medicinal chemists is to identify and validate novel and effective kinase targets for treatment of cancer. Recent studies have shown that cyclin-dependent kinase 8 (CDK8) is a target for treatment of colorectal, breast, melanoma, and prostate cancers. The crystal structure of CDK8 has been reported, and eutectic interactions have been identified for 24 compounds that target CDK8. To more effectively develop CDK8 inhibitors, particularly those with improved selectivity, we summarized the structure, structure-activity relationships, and binding information of typical CDK8 inhibitors, which may serve as a reference for development of novel CDK8 inhibitors.

Keywords: Binding information; CDK8; Inhibitors; Protein kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cyclin-Dependent Kinase 8 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 8 / chemistry
  • Cyclin-Dependent Kinase 8 / metabolism
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8