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. Lue, J. 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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60 Citations
Highly Influential Citations
2
Background Citations
22
Methods Citations
1

60 Citations

EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications

EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which along with other PRC2 components mediates gene expression suppression via the methylation of Histone H3 at lysine 27.…

EZH2-Targeted Therapies in Cancer: Hype or a Reality

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

Targeting Enhancer of Zeste Homolog 2 for the Treatment of Hematological Malignancies and Solid Tumors: Candidate Structure-Activity Relationships Insights and Evolution Prospects.

TLDR
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.

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

TLDR
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.

Hypomethylating Agents in Lymphoma

TLDR
Investigation of DNMT inhibitors as a means of improving responsiveness to chemotherapy in DLBCL patients, or as monotherapy or in combination with other epigenetic agents in the treatment of TCL, concludes that new treatment options that target the pathogenesis of disease are needed.

BET and EZH2 Inhibitors: Novel Approaches for Targeting Cancer

TLDR
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

TLDR
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.

TLDR
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

TLDR
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).

EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas.

...

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