Related Experiment Video

Updated: Sep 18, 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

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A comprehensive description of cyclin-dependent kinase 8 (CDK8) inhibitors as anticancer agents

Ying Liu1, Luhan Sun1, Hongyuan Lu2

  • 1Department of China Medical University-The Queen's University of Belfast Joint College, China Medical University, Shenyang, PR China.

Bioorganic & Medicinal Chemistry
|June 24, 2025
PubMed

Insights

Cyclin-dependent Kinase 8 (CDK8) is a promising target for cancer therapies. This review details selective CDK8 inhibitors, their structures, and structure-activity relationships to guide future drug development.

Area of Science:

  • Molecular Biology
  • Cancer Therapeutics
  • Medicinal Chemistry

Background:

  • Cyclin-dependent Kinase 8 (CDK8) regulates gene transcription via mediator complexes and transcription factor phosphorylation.
  • CDK8 is implicated in tumor progression, including invasion, metastasis, and drug resistance, particularly under radiotherapy stress.
  • Its critical roles in diverse cancers highlight CDK8 as a significant therapeutic target.

Purpose of the Study:

  • To systematically review and analyze various classes of selective CDK8 inhibitors.
  • To examine the structural characteristics and structure-activity relationships (SARs) of these inhibitors.
  • To provide insights for designing more potent, selective, and drug-like CDK8 inhibitors for cancer treatment.

Main Methods:

  • Systematic literature review of selective CDK8 inhibitors.
  • Analysis of inhibitor structural features.
  • Evaluation of structure-activity relationships (SARs).

Main Results:

  • Identification and categorization of different classes of selective CDK8 inhibitors.
  • Detailed analysis of their structural diversity and SARs.
  • Summary of key findings relevant to inhibitor design.

Conclusions:

  • Selective CDK8 inhibitors represent a promising therapeutic strategy for various cancers.
  • Understanding SARs is crucial for optimizing inhibitor potency and selectivity.
  • This review offers guidance for the rational design of next-generation CDK8-targeted cancer drugs.
Keywords:
CDK8 inhibitorsCancersPharmacological activitiesStructural modificationStructure-activity relationship (SAR)

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