Dual-target EZH2 inhibitor: latest advances in medicinal chemistry

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.