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Updated: Jun 13, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
A complex task? Direct modulation of transcription factors with small molecules
1Broad Institute of Harvard and MIT, Chemical Biology Program, 7 Cambridge Center, Cambridge, MA 02142, USA. koehler@broadinstitute.org
Current Opinion in Chemical Biology
|April 17, 2010
Summary
Transcription factors are key drivers of disease, but targeting them with drugs has been difficult. This review highlights new small-molecule drugs that can modulate transcription factor activity, challenging the idea that they are undruggable.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Aberrant transcription factor activity is implicated in various diseases, especially cancer.
- Targeting transcription factors for therapeutic intervention is challenging due to the complexity of protein-protein and protein-DNA interactions.
- The 'undruggable' nature of transcription factors has limited therapeutic development.
Purpose of the Study:
- To review recent advancements in developing small-molecule probes for transcription factors.
- To present evidence challenging the perception of transcription factors as chemically intractable targets.
- To explore the therapeutic potential of modulating transcription factor activity in disease, particularly oncology.
Main Methods:
- Literature review of recent studies on small-molecule transcription factor modulators.
- Analysis of strategies for disrupting or recruiting protein-protein and protein-DNA interactions.
- Synthesis of evidence demonstrating the druggability of transcription factors.
Main Results:
- Significant progress has been made in designing small molecules that modulate transcription factor function.
- Examples of successful small-molecule probes targeting specific transcription factors are emerging.
- These developments provide a strong basis for reconsidering transcription factors as viable drug targets.
Conclusions:
- Transcription factors, despite historical challenges, are increasingly druggable targets.
- Small-molecule probes offer a promising avenue for therapeutic development in diseases driven by aberrant transcription factor activity.
- Further research in this area holds significant potential for novel oncology treatments.
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