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Updated: Mar 23, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Discovery of a small-molecule binder of the oncoprotein gankyrin that modulates gankyrin activity in the cell

Anasuya Chattopadhyay1, Cornelius J O'Connor2, Fengzhi Zhang2

  • 1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1PD, UK.

Scientific Reports
|April 6, 2016
PubMed

Insights

Researchers discovered cjoc42, a small molecule that inhibits gankyrin oncoprotein activity. This finding shows gankyrin is a druggable target, offering a new anticancer strategy by stabilizing tumor suppressor protein p53.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Gankyrin is an oncoprotein linked to various cancers.
  • Overexpressed gankyrin promotes cancer by degrading tumor suppressor protein p53.
  • Targeting gankyrin's protein-protein interactions (PPIs) is a promising anticancer strategy.

Purpose of the Study:

  • To discover small molecules that inhibit gankyrin activity.
  • To investigate the potential of gankyrin as a druggable target for cancer therapy.

Main Methods:

  • Screening for small molecules that bind to gankyrin.
  • Utilizing cell-based assays to assess cjoc42's effect on gankyrin activity.
  • Evaluating cjoc42's impact on p53 protein levels and p53-dependent transcription.

Main Results:

  • A novel small molecule, cjoc42, was identified that binds to gankyrin.
  • Cjoc42 inhibits gankyrin activity in a dose-dependent manner.
  • Cjoc42 prevents p53 degradation, restores p53-dependent transcription, and enhances sensitivity to DNA damage.

Conclusions:

  • Gankyrin is a druggable target for small molecule inhibitors.
  • Cjoc42 represents a potential therapeutic lead for anticancer drug development.
  • Inhibiting gankyrin may offer a novel strategy to stabilize p53 and combat cancer.

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