Wang Xiu-Xiu, Wan Ren-Zhong, Liu Zhao-Peng
Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
College of Animal Science & Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, PR China.
Eur J Med Chem. 2018 Jan 1;143:1406-1418. doi: 10.1016/j.ejmech.2017.10.040. Epub 2017 Oct 16.
Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein trafficking and degradation, cell shape and migration. Selective HDAC6 inhibitors are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Therefore, extensive investigations have been made in the discovery of selective HDAC6 inhibitors. Based on their different zinc binding groups (ZBGs), in this review, HDAC6 inhibitors are grouped as hydroxamic acids, a sulfur containing ZBG based derivatives and other ZBG-derived compounds, and their enzymatic inhibitory activity, selectivity and other biological activities are introduced and summarized.
组蛋白去乙酰化酶HDAC6是IIb类HDAC家族的成员，在HDAC酶中独一无二，具有两个活性催化结构域，并具有独特的生理功能。除了组蛋白修饰外，HDAC6还靶向包括α-微管蛋白和HSP90在内的特定底物，并参与蛋白质运输和降解、细胞形态和迁移。由于HDAC6参与了与神经退行性疾病、癌症和免疫学相关的不同途径，选择性HDAC6抑制剂是一类新兴的药物。因此，在选择性HDAC6抑制剂的发现方面已经进行了广泛的研究。基于它们不同的锌结合基团（ZBGs），在本综述中，HDAC6抑制剂被分为异羟肟酸、含硫ZBG基衍生物和其他ZBG衍生化合物，并介绍和总结了它们的酶抑制活性、选择性和其他生物学活性。
