School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, China.
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, China.
Eur J Med Chem. 2020 Dec 15;208:112831. doi: 10.1016/j.ejmech.2020.112831. Epub 2020 Sep 12.
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.
组蛋白去乙酰化酶（HDACs）是一类能够从组蛋白的 ε-N-乙酰赖氨酸上移除乙酰基的酶，使组蛋白能够更紧密地缠绕 DNA。HDACs 在许多生物学过程中发挥着重要作用，如基因调控、转录、细胞增殖、血管生成、迁移、分化和转移。因此，HDACs 是抗癌药物发现的一个极好的靶点。在过去的十年中，人们加强了对组蛋白去乙酰化酶抑制剂（HDACis）的研究，发现了许多 HDACis，其中一些已经进入市场。然而，目前可用的 HDACis 大多是非同工型选择性的，并且存在一些缺点，如疗效有限、耐药性和毒性。因此，在过去的 5 年中，同工型选择性 HDACis 和具有双重靶向能力的 HDACis 引起了学术界和工业界的广泛关注，并在这一领域取得了重大进展。本文总结了具有双重靶向能力的 HDACis 的最新进展及其在癌症治疗中的潜在应用。
