Inducing protein degradation by proteolysis targeting chimera (PROTAC) has provided great opportunities for scientific research and industrial applications. Histone deacetylase (HDAC)-PROTAC has been widely developed since the first report of its ability to induce the degradation of SIRT2 in 2017. To date, ten of the eighteen HDACs (HDACs 1–8, HDAC10, and SIRT2) have been successfully targeted and degraded by HDAC-PROTACs. HDAC-PROTACs surpass traditional HDAC inhibitors in many aspects, such as higher selectivity, more potent antiproliferative activity, and the ability to disrupt the enzyme-independent functions of a multifunctional protein and overcome drug resistance. Rationally designing HDAC-PROTACs is a main challenge in development because slight variations in chemical structure can lead to drastic effects on the efficiency and selectivity of the degradation. In the future, HDAC-PROTACs can potentially be involved in clinical research with the support of the increased amount of in vivo data, pharmacokinetic evaluation, and pharmacological studies.

通过蛋白水解靶向嵌合体（PROTAC）诱导蛋白质降解为科学研究和工业应用提供了巨大的机会。自 2017 年首次报道其能够诱导 SIRT2 降解以来，组蛋白脱乙酰酶 (HDAC)-PROTAC 得到了广泛的开发。迄今为止，18 个 HDAC 中的 10 个（HDAC 1-8、HDAC10 和 SIRT2）已成功被靶向并被 HDAC-PROTAC 降解。HDAC-PROTAC 在许多方面超越了传统的 HDAC 抑制剂，例如更高的选择性、更有效的抗增殖活性以及破坏多功能蛋白的酶独立功能并克服耐药性的能力。合理设计 HDAC-PROTAC 是开发中的一个主要挑战，因为化学结构的微小变化可能会对降解效率和选择性产生巨大影响。未来，在体内数据量增加、药代动力学评估和药理研究的支持下，HDAC-PROTAC有可能参与临床研究。