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组蛋白去乙酰化酶(HDAC)抑制剂在癌症中的应用:专利研究进展(2017 年至今)。

Histone deacetylase (HDAC) inhibitors in cancer: a patent review (2017-present).

机构信息

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, China.

出版信息

Expert Opin Ther Pat. 2020 Apr;30(4):263-274. doi: 10.1080/13543776.2020.1725470. Epub 2020 Feb 5.

Abstract

: Histone deacetylase (HDAC) inhibitors play a crucial role in restoring the balance of acetylation and deacetylation of lysine residues of histones and non-histone proteins, which are applied to treat several diseases including cancer.: This review covers recent efforts in the synthesis and applications of inhibitors and hybrid inhibitors targeting HDAC from 2017 to 2019.: HDACs are important epigenetic targets and HDAC inhibitors have become important biologically active compounds for the treatment of cancers. Among the recent patents available, most of them place emphasis on HDAC selective inhibitors and multitarget HDAC inhibitors. Although great accomplishments have been achieved in developing HDAC selective inhibitors, there is still an urgent need for discovery of novel HDAC inhibitors with new zinc-binding groups avoiding the unfavorable pharmacokinetics profiles of hydroxamic acid. Apart from cancer therapy, HDAC inhibitors have recently been considered as a new strategy in treating other human diseases, such as alcohol use disorder (AUD), neurological disorders, age-related diseases, and so forth.

摘要

组蛋白去乙酰化酶(HDAC)抑制剂在恢复赖氨酸残基乙酰化和去乙酰化的平衡中起着关键作用,这在治疗包括癌症在内的多种疾病中得到了应用。本综述涵盖了 2017 年至 2019 年针对 HDAC 的抑制剂和混合抑制剂的合成和应用的最新进展。HDAC 是重要的表观遗传靶标,HDAC 抑制剂已成为治疗癌症的重要生物活性化合物。在最近可用的专利中,大多数专利都侧重于 HDAC 选择性抑制剂和多靶点 HDAC 抑制剂。尽管在开发 HDAC 选择性抑制剂方面取得了巨大成就,但仍然迫切需要发现具有新型锌结合基团的新型 HDAC 抑制剂,以避免羟肟酸的不利药代动力学特征。除了癌症治疗外,HDAC 抑制剂最近也被认为是治疗其他人类疾病的一种新策略,如酒精使用障碍(AUD)、神经紊乱、与年龄相关的疾病等。

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