Histone deacetylases (HDACs) are a class of enzymes that remove acetyl from the ε-N-acetyl lysine of histones, allowing histones to wrap DNA more tightly. HDACs play an essential role in many biological processes such as gene regulation, transcription, cell proliferation, angiogenesis, migration, differentiation and metastasis. As a result, HDACs represent an excellent target for anti-cancer drug discovery. The search for histone deacetylase inhibitors (HDACis) has been intensified in the last decade with numerous HDACis being discovered, and some of them have reached the market. However, currently available HDACis are mostly non-isoform selective and suffer from several drawbacks such as limited efficacy, drug resistance, and toxicities. Therefore, isoform-selective HDACis and HDACis with dual targeting capabilities have attracted much attention from academia to industry in the past 5 years, and great advances have been achieved in this area. In this paper, we summarize recent progress on HDACis with dual targeting capabilities and their potential application to cancer treatment.

组蛋白脱乙酰基酶（HDAC）是一类可从ε- N去除乙酰基的酶组蛋白的-乙酰赖氨酸，使组蛋白更紧密地包裹DNA。HDAC在许多生物过程中发挥重要作用，例如基因调节，转录，细胞增殖，血管生成，迁移，分化和转移。结果，HDACs是抗癌药物发现的极佳靶标。在过去的十年中，对组蛋白脱乙酰基酶抑制剂（HDACis）的搜寻已得到加强，发现了许多HDACis，其中一些已进入市场。但是，当前可用的HDACis大多是非异构体选择性的，并且具有一些缺点，例如功效有限，耐药性和毒性。因此，过去5年中，具有双重靶向功能的同工型选择性HDACis和HDACis引起了学术界和工业界的广泛关注，在这方面已经取得了很大的进步。在本文中，我们总结了具有双重靶向功能的HDACis的最新进展及其在癌症治疗中的潜在应用。