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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61 Citations
Highly Influential Citations
2
Background Citations
23
Methods Citations
1

61 Citations

EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications

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This review highlights the recent advances in targeting EZH2, its successes, and potential limitations, and discusses the future directions of this therapeutic subclass.

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This article systematically reviews the research progress on EZH2 inhibitors and proteolysis targeting chimera (PROTAC)-based EZh2 degradation agents with a focus on their design strategies, structure-activity relationships (SARs), and safety and clinical manifestations.

Histone Deacetylase and Enhancer of Zeste Homologue 2 Dual Inhibitors Presenting a Synergistic Effect for the Treatment of Hematological Malignancies.

Compound 20 exhibited excellent inhibitory activity against HDAC1 and EZH2 and showed good antiproliferation activity against MV4-11, which suggested that 20 may be a promising drug candidate for treating hematological malignancies.

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

The existing knowledge of synthetic lethal relationships between EZH2/PRC2 and components of the SWI/SNF complex is summarized and the potential application of existing EZh2 inhibitors in cancer patients harboring mutations in SWI-SNF proteins is discussed.

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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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