HDAC8 as a target in drug discovery: Function, structure and design.

Autor: Zhao Q; 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., Liu H; The People's Hospital of Zhaoyuan City, No. 168 Yingbin Road, Zhaoyuan, 265400, Shandong Province, PR China., Peng J; 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., Niu H; 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., Liu J; 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., Xue H; 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., Liu W; 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., Liu X; 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., Hao H; 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., Zhang X; 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., Wu J; 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. Electronic address: wujingde70@sdu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2024 Dec 15; Vol. 280, pp. 116972. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1016/j.ejmech.2024.116972
Abstrakt: Histone deacetylases (HDACs) have emerged as prominent therapeutic targets in drug discovery. Among the members of the HDAC family, HDAC8 exhibits distinct structural and physiological features from other members of the class Ⅰ HDACs. In addition to histones, numerous non-histone substrates such as structural maintenance of chromosomes 3 (SMC3), p53, estrogen-related receptor alpha (ERRα), etc., have been identified for HDAC8, suggesting the involvement of HDAC8 in diverse biological processes. Studies have demonstrated that HDAC8 plays essential roles in certain disease development, e.g., acute myeloid leukemia (AML), neuroblastoma, and X-Linked disorders. Despite several HDAC8 inhibitors have been discovered, only one compound has progressed to clinical studies. Recently, novel strategies targeting HDAC8 have emerged, including identifying innovative zinc-chelating groups (ZBG), developing multi-target drugs, and HDAC8 PROTACs. This review aims to summarize recent progress in developing new HDAC8 inhibitors that incorporate novel strategies and provide an overview of the clinical improvements associated with HDAC8 inhibitors.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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