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Structural classification of EZH2 inhibitors and prospects for the treatment of tumor: a review

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Abstract

Zeste homolog enhancer 2 (EZH2) is one of the core catalytic subunits of PRC2, which mainly mediates histone H3K27 trimethylation to regulate the expression of tumor suppressor genes. Tazemetostat has been approved by the FDA as the first EZH2 inhibitor for the treatment of epithelioid sarcoma in 2020. In recent years, the role of EZH2 in tumor pathophysiology has been further studied, and more and more novel EZH2 inhibitors have been reported and applied in the treatment of lymphoma, prostate cancer, lung cancer and other cancers. In this article, we analyzed and summarized the structural features and the biological activity of various novel EZH2 inhibitors reported since 2018. Simultaneously, we reclassified the reported novel EZH2 inhibitors from the perspective of structure, and discussed their ability to treat malignant tumors and their future development trend. These provides a new strategy for the research of EZH2 inhibitors in medicinal chemistry.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No.82204210), the Biological Medicine Joint Fund of Natural Science Foundation of Hebei Province (NO. H2022406062), the Funded by Science and Technology Project of Hebei Education Department (NO. QN2022161), the 2022 Research Start‐up Fund for High‐level Talents of Chengde Medical University (NO. 202207), and the Chengde Medical University basic research funds special project (NO. KY202315).

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  1. These authors contributed equally: Ling Yu, Ming-tao Xia

Authors and Affiliations

  1. Department of Pharmacy, Anorectal Hospital of Chengde Medical University, Chengde, 067000, PR China

    Ling Yu

  2. Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, 067000, PR China

    Ming-tao Xia, You-de Wang, Zhi-wei Yan, Li-ying Zhang & Shuai Li

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Yu, L., Xia, Mt., Wang, Yd. et al. Structural classification of EZH2 inhibitors and prospects for the treatment of tumor: a review. Med Chem Res 32, 1589–1604 (2023). https://doi.org/10.1007/s00044-023-03105-y

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