Related Experiment Video

Updated: Dec 25, 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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Synthesis and biological evaluation of small molecule modulators of CDK8/Cyclin C complex with phenylaminoquinoline

Mohammad M Al-Sanea1

  • 1Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Sakaka, Aljouf, Saudi Arabia.

Peerj
|March 25, 2020
PubMed
Abstract

Insights

The cyclin-dependent kinase 8/cyclin C (CDK8/CycC) complex is implicated in cancer. Researchers synthesized novel 4-phenylaminoquinoline compounds, identifying potent CDK8/CycC inhibitors for cancer therapy.

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Cancer Research

Background:

  • The CDK8/CycC complex regulates transcription and is overexpressed in human malignancies, acting as a cancer oncogene.
  • CDK8/CycC complex is a potential therapeutic target for cancer treatment.
  • The mediator complex is involved in transcription regulation by CDK8/CycC.

Purpose of the Study:

  • To synthesize and evaluate 4-phenylaminoquinoline derivatives as potential inhibitors of the CDK8/CycC complex.
  • To explore structure-activity relationships of these compounds for cancer therapy.

Main Methods:

  • Synthesis of nine 4-phenylaminoquinoline scaffold-based compounds (5a-i).
  • Biological evaluation of synthesized compounds as CDK8/CycC complex inhibitors.

Main Results:

  • The study investigated substituent effects on CDK8/CycC inhibitory activity.
  • Secondary benzenesulfonamide analogues demonstrated the most potent inhibition of CDK8/CycC.
  • Primary and reversed sulfonamide analogues showed significantly lower or no activity.

Conclusions:

  • The 4-phenylaminoquinoline scaffold exhibits promising CDK8/CycC inhibitory activity.
  • The sulfonamido group's substitution pattern is critical for inhibitory activity.
  • Compound 5d showed submicromolar potency (IC50 = 0.639 µM) and warrants further investigation for drug design.
Keywords:
ActivityBiological evaluationCDK8/CycCCancerDesignKinase inhibitionQuinolineSeriesSulfonamideSynthesis

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