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Updated: Dec 28, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

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Binding patterns and structure-activity relationship of CDK8 inhibitors

Duo Ma1, Xing Chen1, Xiao-Bao Shen2

  • 1School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, PR China.

Bioorganic Chemistry
|February 21, 2020
PubMed

Insights

Cyclin-dependent kinase 8 (CDK8) is a promising cancer target. This review summarizes CDK8 inhibitors, aiding the development of more selective cancer drugs.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Structural Biology

Background:

  • Cyclin-dependent kinase 8 (CDK8) is an emerging therapeutic target for various cancers, including colorectal, breast, melanoma, and prostate.
  • The crystal structure of CDK8 has been elucidated, revealing potential binding sites for inhibitors.
  • Eutectic interactions have been identified for 24 known CDK8-targeting compounds.

Purpose of the Study:

  • To consolidate information on CDK8 inhibitors to guide the development of novel therapeutic agents.
  • To provide a reference for medicinal chemists focusing on CDK8 inhibitor design, emphasizing improved selectivity.
  • To analyze structure-activity relationships and binding data of existing CDK8 inhibitors.

Main Methods:

  • Literature review and data compilation on CDK8 inhibitors.
  • Analysis of published crystal structures of CDK8.
  • Summary of structure-activity relationships (SAR) and binding data for identified compounds.

Main Results:

  • Identification and characterization of 24 compounds exhibiting eutectic interactions with CDK8.
  • Detailed summary of the structural features and activity profiles of representative CDK8 inhibitors.
  • Analysis of SAR trends and binding modes for various inhibitor classes.

Conclusions:

  • CDK8 is a validated target for multiple cancer types.
  • Understanding the structure, SAR, and binding of current inhibitors is crucial for designing next-generation CDK8-targeted cancer therapies.
  • This review serves as a valuable resource for researchers aiming to develop more selective and effective CDK8 inhibitors.
Keywords:
Binding informationCDK8InhibitorsProtein kinases

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