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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Using Chemical Epigenetics to Target Cancer.

Virangika K Wimalasena1, Tingjian Wang2, Logan H Sigua1

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

Molecular Cell
|May 15, 2020
PubMed
Summary

Targeting epigenetic proteins offers new cancer therapies by controlling gene transcription. Advances in chemical biology and PROTAC technology yield promising preclinical compounds with reduced toxicity.

Keywords:
PROTACchromatindegraderepigeneticsinhibitorpeptidomimetictranscription

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Chemical Biology

Background:

  • Transcription is epigenetically controlled by chromatin-binding proteins.
  • These proteins regulate gene expression essential for normal and malignant cell states.
  • Targeting epigenetic proteins is a promising therapeutic strategy, especially in oncology.

Purpose of the Study:

  • To review recent advances in targeting epigenetic proteins for therapeutic translation.
  • To explore novel strategies for modulating transcription with reduced toxicity.
  • To highlight the potential of chemical biology and functional genomics in drug development.

Main Methods:

  • Review of conventional active site and allosteric inhibitors.
  • Exploration of peptidomimetics in epigenetic drug discovery.
  • Analysis of proteolysis-targeted chimera (PROTAC) technology for targeting epigenetic proteins.

Main Results:

  • Advances in chemical biology and functional genomics enable targeted epigenetic therapies.
  • Development of effective strategies to modulate transcription with reduced off-target effects.
  • Promising preclinical compounds identified through novel targeting approaches.

Conclusions:

  • Targeting epigenetic regulators offers a viable therapeutic avenue, particularly for cancer treatment.
  • Novel technologies like PROTACs are expanding the possibilities for epigenetic drug development.
  • Continued research in chemical biology and functional genomics will drive therapeutic translation.