新型 HDAC 抑制剂的药物化学研究进展（2020 年至今）。
Medicinal chemistry updates of novel HDACs inhibitors (2020 to present).
机构信息
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; School of Pharmacy, Liaocheng University, Shandong, 252000, China; Hunan Engineering Technology Research Center for Comprehensive Development and Utilization of Biomass Resources, Hunan University of Science and Engineering, Yongzhou, 425199, China.
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
出版信息
Eur J Med Chem. 2022 Jan 5;227:113946. doi: 10.1016/j.ejmech.2021.113946. Epub 2021 Oct 22.
Epigentic enzymes histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-N-acetylated lysine residues of various protein substrates including both histone and non-histone proteins. Different HDACs have distinct biological functions and are recruited to specific regions of the genome. Due to their important biological functions, HDACs have been validated in clinics for anticancer therapy, and are being explored for potential treatment of several other diseases such as Alzheimer disease (AD), metabolic disease, viral infection, and multiple sclerosis, etc. Besides five approved drugs, there are more than thirty HDACs inhibitors currently being investigated in clinical trials. Centering on the advances of drug discovery programs in this field since 2020, this review discusses HDACs inhibitors from the aspects of the structure-based rational design, isoform selectivity, pharmacology, and toxicology of the compounds of interest. The hope is to provide the medicinal chemistry community with up-to-date information and to accelerate the drug discovery programs in this area.
表观遗传酶组蛋白去乙酰化酶（HDACs）催化各种蛋白底物中 ε-N-乙酰化赖氨酸残基上乙酰基的去除，这些蛋白底物包括组蛋白和非组蛋白。不同的 HDACs 具有不同的生物学功能，并被招募到基因组的特定区域。由于其重要的生物学功能，HDACs 已在临床上被验证可用于抗癌治疗，并正在探索其在治疗阿尔茨海默病（AD）、代谢疾病、病毒感染和多发性硬化症等多种其他疾病方面的潜在用途。除了 5 种已批准的药物外，目前还有 30 多种 HDAC 抑制剂正在临床试验中进行研究。本文围绕 2020 年以来该领域药物发现计划的进展，从基于结构的合理设计、同型选择性、化合物的药理学和毒理学等方面讨论了 HDAC 抑制剂。希望为药物化学界提供最新信息，并加速该领域的药物发现计划。
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