靶向HDAC6的选择性抑制剂作为抗癌药物的最新进展：结构、功能与设计

Recent development of selective inhibitors targeting the HDAC6 as anti-cancer drugs: Structure, function and design.

作者信息

Peng Jie, Xie Fei, Qin Pengxia, Liu Yujing, Niu Haoqian, Sun Jie, Xue Haoyu, Zhao Qianlong, Liu Jingqian, Wu Jingde

机构信息

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.

Department of Pharmacy, Qilu Hospital of Shandong University, Jinan 250012, PR China.

出版信息

Bioorg Chem. 2023 Sep;138:106622. doi: 10.1016/j.bioorg.2023.106622. Epub 2023 May 22.

DOI:10.1016/j.bioorg.2023.106622

PMID:37244230

Abstract

HDAC6, a member of the histone deacetylase family, mainly is a cytosolic protein and regulates cell growth by acting on non-histone substrates, such as α -tubulin, cortactin, heat shock protein HSP90, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), that are closely related to the proliferation, invasion, immune escape and angiogenesis of cancer tissues. The approved drugs targeting the HDACs are all pan-inhibitors and have many side effects due to their lack of selectivity. Therefore, development of selective inhibitors of HDAC6 has attracted much attention in the field of cancer therapy. In this review, we will summarize the relationship between HDAC6 and cancer, and discuss the design strategies of HDAC6 inhibitors for cancer treatment in recent years.

摘要

组蛋白去乙酰化酶6（HDAC6）是组蛋白去乙酰化酶家族的成员之一，主要是一种胞质蛋白，通过作用于非组蛋白底物（如α-微管蛋白、皮层肌动蛋白、热休克蛋白HSP90、程序性死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1））来调节细胞生长，这些底物与癌组织的增殖、侵袭、免疫逃逸和血管生成密切相关。已获批的靶向HDACs的药物均为泛抑制剂，由于缺乏选择性而具有许多副作用。因此，HDAC6选择性抑制剂的开发在癌症治疗领域备受关注。在本综述中，我们将总结HDAC6与癌症之间的关系，并讨论近年来用于癌症治疗的HDAC6抑制剂的设计策略。