Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifying enzymes in pathological conditions. Over the past two decades, a growing array of small molecule drugs targeting epigenetic enzymes such as DNA methyltransferase, histone deacetylase, isocitrate dehydrogenase, and enhancer of zeste homolog 2, have been thoroughly investigated and implemented as therapeutic options, particularly in oncology. Additionally, numerous epigenetics-targeted drugs are undergoing clinical trials, offering promising prospects for clinical benefits. This review delineates the roles of epigenetics in physiological and pathological contexts and underscores pioneering studies on the discovery and clinical implementation of epigenetics-targeted drugs. These include inhibitors, agonists, degraders, and multitarget agents, aiming to identify practical challenges and promising avenues for future research. Ultimately, this review aims to deepen the understanding of epigenetics-oriented therapeutic strategies and their further application in clinical settings.

表观遗传学通过五个关键机制控制染色质状态调节系统：DNA 修饰、组蛋白修饰、RNA 修饰、染色质重塑和非编码 RNA 调控。这些机制及其相关酶独立于 DNA 碱基序列传递遗传信息，在生物体发育和体内平衡中起着重要作用。相反，表观遗传景观的破坏对各种人类疾病的发病机制产生重大影响。这种理解为开发在病理条件下靶向表观遗传学修饰酶的药物奠定了坚实的理论基础。在过去的二十年里，越来越多的靶向表观遗传酶（如 DNA 甲基转移酶、组蛋白脱乙酰酶、异柠檬酸脱氢酶和 zeste 同源物增强子 2）的小分子药物已被彻底研究并作为治疗选择实施，尤其是在肿瘤学中。此外，许多表观遗传学靶向药物正在进行临床试验，为临床益处提供了广阔的前景。本综述描述了表观遗传学在生理和病理背景下的作用，并强调了关于表观遗传学靶向药物发现和临床实施的开创性研究。这些药物包括抑制剂、激动剂、降解剂和多靶点药物，旨在确定未来研究的实际挑战和有希望的途径。最终，本综述旨在加深对以表观遗传学为导向的治疗策略及其在临床环境中的进一步应用的理解。