Related Experiment Video

Updated: Jul 4, 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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Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

Alexandre Bancet1,2, Rita Frem3, Florian Jeanneret4

  • 1University Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Institut Convergence Plascan, Team « Small Molecules for Biological Targets », 69373 Lyon, France.

Iscience
|February 6, 2024
PubMed

Insights

A novel selective inhibitor, AB668, targets protein kinase CK2 via a unique bivalent binding mode. This inhibitor demonstrates distinct anti-cancer activity by inducing apoptosis and modulating specific pathways in renal cell carcinoma.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Protein kinase CK2 (CK2) is implicated in various cancers.
  • There is a need for selective CK2 inhibitors to study its role in cancer and for therapeutic development.

Purpose of the Study:

  • To discover and characterize a novel, selective CK2 inhibitor.
  • To compare the anti-cancer mechanism of the new inhibitor with existing ones.

Main Methods:

  • Discovery of AB668, a bivalent CK2 inhibitor.
  • Caspase activation assays, live-cell imaging, and transcriptomic analysis.
  • Comparison with ATP-competitive inhibitors CX-4945 and SGC-CK2-1.

Main Results:

  • AB668 exhibits selective bivalent binding to CK2 at the ATP site and the unique αD pocket.
  • AB668 induces apoptotic cell death in multiple cancer cell lines.
  • AB668 displays a distinct mechanism of action compared to CX-4945 and SGC-CK2-1, modulating specific pathways in renal cell carcinoma.

Conclusions:

  • AB668 represents a novel bivalent inhibitor with a distinct mechanism for targeting CK2.
  • This inhibitor offers a valuable tool for investigating CK2's role in cancer and its therapeutic potential.
Keywords:
CancerCell biologyMolecular biologyStructural biology

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