State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Department of Orthodontics, Sichuan University, Chengdu, 610041, Sichuan, China.
Future Med Chem. 2024 Aug 2;16(15):1561-1582. doi: 10.1080/17568919.2024.2380243. Epub 2024 Jul 31.
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(), 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.
增强子结合锌指蛋白 2（EZH2）是一种组蛋白甲基转移酶，通过调节基因表达在肿瘤进展中发挥关键作用。EZH2 抑制剂因其在癌症治疗策略中的潜力而成为有前途的抗肿瘤药物。然而，单靶抑制剂常常面临耐药性和副作用等限制。双靶抑制剂，如 EZH1/2 抑制剂 HH-2853（），提供了增强的疗效和降低的不良反应。本综述强调了针对 EZH2 和其他蛋白质（如 BRD4、PARP1 和 EHMT2）的双抑制剂的最新进展，强调了合理设计、结构-活性关系和安全性概况，表明它们在临床应用中的潜力。
