Department of Pharmacy, Shandong Second Provincial General Hospital, Jinan, Shandong, China.
Department of Medicinal Chemistry, School of Pharmacy, Qingdao University Medical College, Qingdao University, Qingdao, Shandong, China.
Mini Rev Med Chem. 2024;24(5):480-490. doi: 10.2174/1389557523666230717110255.
Histone deacetylases (HDACs) are a class of enzymes that are responsible for the removal of acetyl groups 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, which make it an excellent target for anticancer drug discovery. The search for histone deacetylase inhibitors (HDACis) has been intensified, with numerous HDACis being discovered, and five of them have reached the market. However, currently available HDAC always suffers from several shortcomings, such as limited efficacy, drug resistance, and toxicity. Accordingly, dual-targeting HDACis have attracted much attention from academia to industry, and great advances have been achieved in this area. In this review, we summarize the progress on inhibitors with the capacity to concurrently inhibit tubulin polymerization and HDAC activity and their application in cancer treatment.
组蛋白去乙酰化酶（HDACs）是一类酶，负责从组蛋白的ε-N-乙酰赖氨酸上除去乙酰基，使组蛋白能够更紧密地包裹 DNA。HDACs 在许多生物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，这使其成为抗癌药物发现的理想靶点。寻找组蛋白去乙酰化酶抑制剂（HDACis）的工作已经得到了加强，已经发现了许多 HDACis，其中有 5 种已经上市。然而，目前可用的 HDAC 总是存在一些缺点，如疗效有限、耐药性和毒性。因此，双重靶向 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。在这篇综述中，我们总结了同时抑制微管聚合和 HDAC 活性的抑制剂的进展及其在癌症治疗中的应用。
