Dual-target EZH2 inhibitor: latest advances in medicinal chemistry

被引：3

作者：

Wei, Lai ^{[1
,2
,3
]}

Mei, Dan ^{[1
,2
,3
]}

Hu, Sijia ^{[1
,2
,3
]}

Du, Shufang ^{[1
,2
,3
]}

机构：

[1] Sichuan Univ, West China Hosp, State Key Lab Oral Dis, Stomatol Dept Orthodont, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Univ, Natl Ctr Stomatol, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Sichuan, Peoples R China

来源：

FUTURE MEDICINAL CHEMISTRY | 2024年 / 16卷 / 15期

关键词：

AR; BMI1; DNMTs; drug design; EHMT2 (G9a); EZH2; inhibitors; structure-activity relationship; SMALL-MOLECULE INHIBITOR; GROUP PROTEIN EZH2; HOMOLOG; EZH2; ANDROGEN RECEPTOR; STEM-CELLS; SELECTIVE-INHIBITION; CANCER-CELLS; POLYCOMB; METHYLATION; COMPLEX;

D O I：

10.1080/17568919.2024.2380243

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays a crucial role in tumor progression by regulating gene expression. EZH2 inhibitors have emerged as promising anti-tumor agents due to their potential in cancer treatment strategies. However, single-target inhibitors often face limitations such as drug resistance and side effects. Dual-target inhibitors, exemplified by EZH1/2 inhibitor HH-2853(28), offer enhanced efficacy and reduced adverse effects. This review highlights recent advancements in dual inhibitors targeting EZH2 and other proteins like BRD4, PARP1, and EHMT2, emphasizing rational design, structure-activity relationships, and safety profiles, suggesting their potential in clinical applications.

引用

页码：1561 / 1582

页数：22

共 132 条

[1] Subtyping of Triple-Negative Breast Cancer: Implications for Therapy [J].

Abramson, Vandana G. ;

Lehmann, Brian D. ;

Ballinger, Tarah J. ;

Pietenpol, Jennifer A. .

CANCER, 2015, 121 (01) :8-16

[2] EZH1/2 as targets for cancer therapy [J].

An, Ran ;

Li, Yu-Qing ;

Lin, Yue-Ling ;

Xu, Fang ;

Li, Man-Mei ;

Liu, Zhong .

CANCER GENE THERAPY, 2023, 30 (02) :221-235

[3] Ezh1 Targets Bivalent Genes to Maintain Self-Renewing Stem Cells in Ezh2-Insufficient Myelodysplastic Syndrome [J].

Aoyama, Kazumasa ;

Oshima, Motohiko ;

Koide, Shuhei ;

Suzuki, Emi ;

Mochizuki-Kashio, Makiko ;

Kato, Yuko ;

Tara, Shiro ;

Shinoda, Daisuke ;

Hiura, Nobuhiro ;

Nakajima-Takagi, Yaeko ;

Sashida, Goro ;

Iwama, Atsushi .

ISCIENCE, 2018, 9 :161-+

[4] Long non-coding RNA SNGH7 Is activated by SP1 and exerts oncogenic properties by interacting with EZH2 in ovarian cancer [J].

Bai, Zhuanli ;

Wu, YinYing ;

Bai, Shuheng ;

Yan, Yanli ;

Kang, Haojing ;

Ma, Wen ;

Zhang, Jiangzhou ;

Gao, Ying ;

Hui, Beina ;

Ma, Hailin ;

Li, Rong ;

Zhang, Xiaozhi ;

Ren, Juan .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2020, 24 (13) :7479-7489

[5] EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation [J].

Beguelin, Wendy ;

Popovic, Relja ;

Teater, Matt ;

Jiang, Yanwen ;

Bunting, Karen L. ;

Rosen, Monica ;

Shen, Hao ;

Yang, Shao Ning ;

Wang, Ling ;

Ezponda, Teresa ;

Martinez-Garcia, Eva ;

Zhang, Haikuo ;

Zheng, Yupeng ;

Verma, Sharad K. ;

McCabe, Michael T. ;

Ott, Heidi M. ;

Van Aller, Glenn S. ;

Kruger, Ryan G. ;

Liu, Yan ;

McHugh, Charles F. ;

Scott, David W. ;

Chung, Young Rock ;

Kelleher, Neil ;

Shaknovich, Rita ;

Creasy, Caretha L. ;

Gascoyne, Randy D. ;

Wong, Kwok-Kin ;

Cerchietti, Leandro ;

Levine, Ross L. ;

Abdel-Wahab, Omar ;

Licht, Jonathan D. ;

Elemento, Olivier ;

Melnick, Ari M. .

CANCER CELL, 2013, 23 (05) :677-692

[6] CHEST ROENTGENOGRAPHY AS A WINDOW TO DIAGNOSIS OF TAKAYASUS ARTERITIS [J].

BERKMEN, YM ;

LANDE, A .

AMERICAN JOURNAL OF ROENTGENOLOGY, 1975, 125 (04) :842-846

[7] A cytosolic Ezh1 isoform modulates a PRC2-Ezh1 epigenetic adaptive response in postmitotic cells [J].

Bodega, Beatrice ;

Marasca, Federica ;

Ranzani, Valeria ;

Cherubini, Alessandro ;

Della Valle, Francesco ;

Neguembor, Maria Victoria ;

Wassef, Michel ;

Zippo, Alessio ;

Lanzuolo, Chiara ;

Pagani, Massimiliano ;

Orlando, Valerio .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2017, 24 (05) :444-+

[8] EZH2 Inhibitor Efficacy in Non-Hodgkin's Lymphoma Does Not Require Suppression of H3K27 Monomethylation [J].

Bradley, William D. ;

Arora, Shilpi ;

Busby, Jennifer ;

Balasubramanian, Srividya ;

Gehling, Victor S. ;

Nasveschuk, Christopher G. ;

Vaswani, Rishi G. ;

Yuan, Chih-Chi ;

Hatton, Charlie ;

Zhao, Feng ;

Williamson, Kaylyn E. ;

Iyer, Priyadarshini ;

Mendez, Jacqui ;

Campbell, Robert ;

Cantone, Nico ;

Garapaty-Rao, Shivani ;

Audia, James E. ;

Cook, Andrew S. ;

Dakin, Les A. ;

Albrecht, Brian K. ;

Harmange, Jean-Christophe ;

Daniels, Danette L. ;

Cummings, Richard T. ;

Bryant, Barbara M. ;

Normant, Emmanuel ;

Trojer, Patrick .

CHEMISTRY & BIOLOGY, 2014, 21 (11) :1463-1475

[9] Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance [J].

Brooun, Alexei ;

Gajiwala, Ketan S. ;

Deng, Ya-Li ;

Liu, Wei ;

Bolanos, Ben ;

Bingham, Patrick ;

He, You-Ai ;

Diehl, Wade ;

Grable, Nicole ;

Kung, Pei-Pei ;

Sutton, Scott ;

Maegley, Karen A. ;

Yu, Xiu ;

Stewart, Al E. .

NATURE COMMUNICATIONS, 2016, 7 :11384

[10] Bmi1 controls tumor development in an ink4a/Arf-independent manner in a mouse model for glioma [J].

Bruggeman, Sophia W. M. ;

Hulsman, Danielle ;

Tanger, Ellen ;

Buckle, Tessa ;

Blom, Marleen ;

Zevenhoven, John ;

van Tellingen, Olaf ;

van Lohuizen, Maarten .

CANCER CELL, 2007, 12 (04) :328-341

← 1 2 3 4 5 6 7 8 9 10 →