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Targeting EZH2 as cancer therapy.

Shunsuke Hanaki1, Midori Shimada1

  • 1Department of Biochemistry, Joint Faculty of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8511, Japan.

Journal of Biochemistry
|January 22, 2021
PubMed
Summary

A novel Enhancer of zeste homolog 2 (EZH2) inhibitor, NPD13668, shows promise for cancer therapy by blocking EZH2 activity and inhibiting cancer cell growth. This review covers PRC2, H3K27me, and emerging EZH2-targeted drugs.

Keywords:
EZH2PRC2histonesrepressortranscription

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Area of Science:

  • Epigenetics and Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2).
  • PRC2 mediates gene repression through histone H3 Lysine 27 trimethylation (H3K27me3).
  • EZH2 plays a significant role in various cancers, making it a therapeutic target.

Purpose of the Study:

  • To review the biological significance of PRC2 and H3K27me.
  • To highlight recent advances in developing drugs targeting PRC2.
  • To introduce NPD13668, a novel EZH2 inhibitor.

Main Methods:

  • High-throughput screening assay to identify EZH2 inhibitors.
  • In vitro assays to assess EZH2 methyltransferase activity.
  • Cell-based assays to evaluate cell growth inhibition in cancer lines.

Main Results:

  • Identification of NPD13668 as a novel EZH2 inhibitor.
  • NPD13668 demonstrated inhibition of EZH2 methyltransferase activity.
  • NPD13668 repressed proliferation in multiple cancer cell lines.

Conclusions:

  • NPD13668 shows potential as a therapeutic agent for cancer treatment.
  • Targeting EZH2 is a promising strategy in oncology.
  • Further development and clinical evaluation of EZH2 inhibitors are warranted.