Emerging EZH2 Inhibitors and Their Application in Lymphoma

@article{Lue2018EmergingEI,
  title={Emerging EZH2 Inhibitors and Their Application in Lymphoma},
  author={Jennifer K. Lue and Jennifer E. Amengual},
  journal={Current Hematologic Malignancy Reports},
  year={2018},
  volume={13},
  pages={369-382}
}
  • J. LueJ. Amengual
  • Published 15 August 2018
  • Biology, Medicine
  • Current Hematologic Malignancy Reports
Purpose of ReviewEnhancer of Zeste Homolog 2 (EZH2) is histone methyltransferase and catalyzes the methylation of histone 3 lysine 27, a mark of transcriptional repression. Various studies have elucidated the complex role of EZH2 in both normal biology and tumorigenesis. Here, we critically review the emerging role of EZH2 in malignancies, the development of small molecule inhibitors of EZH2, and their application in lymphoma.Recent FindingsActivating mutations and overexpression of EZH2 are… 

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Potential of enhancer of zeste homolog 2 inhibitors for the treatment of SWI/SNF mutant cancers and tumor microenvironment modulation

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BET and EZH2 Inhibitors: Novel Approaches for Targeting Cancer

Two new classes of epigenome-targeting agents are reviewed: the bromodomain and extraterminal domain proteins (BET) inhibitors and the enhancer of zeste homolog (EZH2) inhibitors.

Deregulation of Polycomb Repressive Complex-2 in Mantle Cell Lymphoma Confers Growth Advantage by Epigenetic Suppression of cdkn2b

Results highlight that deregulation of PRC2/EZH2 is associated with epigenetic suppression of cdkn2b in MCL, and in part responsible for increased cell growth, thus the EZH 2 inhibitors may have therapeutic potential in the patients with MCL.

Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase.

The discovery of potent and orally bioavailable EED ligands with good solubilities is disclosed, with the resulting compounds exhibiting in vivo efficacy in EZH2-driven tumors.

A chemical strategy toward novel brain-penetrant EZH2 inhibitors

This work has identified a chemical strategy, based on computational modeling of pyridone-containing EZH2 inhibitor scaffolds, to minimize P-glycoprotein activity and reports the first brain-penetrant EZh2 inhibitor, TDI-6118 (compound 5).
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