摘要
背景:组蛋白乙酰化是翻译后修饰(PTM)的重要方法,是由含有Bromodomains的蛋白(BRD)介导的表观遗传调控的重要组成部分。近年来,许多研究人员发现,各种恶性肿瘤,炎症和其他疾病的发生和发展都与BRD4表达障碍或功能障碍有关。同时,在许多论文中已经报道了许多外末端(BET)家族的抑制剂。 目的:本综述总结了新发现的BET抑制剂,其作用机制和生物活性。其次,这些化合物主要根据其结构进行分类,并讨论了它们的结构 - 活性关系信息。除此之外,还指出了每个化合物的设计策略。 结果和结论:在此,报道了最近的进展,发现了更优异的小分子抑制剂。目前,除化合物4外,化合物7,22和90也已进入临床试验阶段。鉴于BET抑制剂在抗肿瘤,抗炎和抗药性方面的突出表现,我们认为越来越多的BET抑制剂将成为临床实践中针对癌症,炎症和自身免疫性疾病的新型表观遗传疗法。不远的将来。
关键词: BET抑制剂,乙酰赖氨酸,转录调节,染色质,BRD,SAR。
图形摘要
Current Drug Targets
Title:Disrupting Acetyl-lysine Interactions: Recent Advance in the Development of BET Inhibitors
Volume: 19 Issue: 10
关键词: BET抑制剂,乙酰赖氨酸,转录调节,染色质,BRD,SAR。
摘要: Background: Histone acetylation is an essential approach of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by Bromodomainscontaining protein (BRDs). In recent years, many researchers have found that a variety of malignancy, inflammatory and other diseases occurrences and developments are associated with BRD4 expression disorders or dysfunction. Meanwhile, many inhibitors of the extra-terminal (BET) family have been reported in many papers.
Objective: This review summarized those newly found BET inhibitors, their mechanism of action and bioactivity. Secondly, those compounds were mainly classified based on their structures and their structure-activity relationship information was discussed. Beyond that, every compound’s design strategy was pointed out.
Results and Conclusion: Herein, the recent advances reported were reviewed for discovering more excellent small molecule inhibitors. Currently, in addition to compound 4, compounds 7, 22 and 90, have also been into the clinical trial stage. In the view of the outstanding performance of BET inhibitors in anti-tumor, anti-inflammatory and anti-drug resistance, we believe that more and more BET inhibitors will become the new epigenetic therapy for cancer, inflammation and autoimmune disease in clinical practice in the near future.
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Cite this article as:
Disrupting Acetyl-lysine Interactions: Recent Advance in the Development of BET Inhibitors, Current Drug Targets 2018; 19 (10) . https://dx.doi.org/10.2174/1389450119666171129165427
DOI https://dx.doi.org/10.2174/1389450119666171129165427 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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