Drugging the 'undruggable'. Therapeutic targeting of protein-DNA interactions with the use of computer-aided drug

Related Experiment Video

Updated: Oct 26, 2025

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
08:31

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

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Mariia Radaeva1, Anh-Tien Ton1, Michael Hsing1

  • 1Vancouver Prostate Centre and the Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.

Drug Discovery Today
|July 31, 2021
PubMed

Insights

Computer-aided drug discovery (CADD) is revolutionizing cancer therapy by enabling the targeting of transcription factors (TFs). Recent CADD successes offer new drug candidates to directly inhibit cancer-driving TF-DNA interactions.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Transcription factors (TFs) are key drivers of cancer, but their protein-DNA interactions are challenging therapeutic targets.
  • Historically, protein-DNA interfaces were considered 'undruggable' by small molecules.

Purpose of the Study:

  • To review recent advancements in computer-aided drug discovery (CADD) for targeting cancer TFs.
  • To highlight successful CADD campaigns and emerging drug candidates.

Main Methods:

  • Review of recent literature on CADD strategies.
  • Analysis of successful drug discovery campaigns targeting specific TFs.

Main Results:

  • Significant progress in CADD has shifted the paradigm of targeting protein-DNA interfaces.
  • Identified drug candidates that directly interfere with TF-DNA binding for key oncogenic TFs.
  • Examples include targeting androgen receptor (AR), ERG, MYC, TOX, TOP2, and STAT3.

Conclusions:

  • CADD offers novel therapeutic strategies for targeting cancer-associated TFs.
  • These approaches open new avenues for treating various cancers and other diseases driven by TFs.
Keywords:
AICancerComputer-aided drug discoveryDrugsProtein–DNA interactionsTranscription factor

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