"Inhibitors of bromodomain and extra‐terminal proteins for treating multiple human diseases." Medicinal research reviews 41.1 (2021): 223-245. 如果您想咨询相关业务或者对其他业务感兴趣,欢迎点击如下链接,联系我们 ⤵️喜欢我们的内容,欢迎关注@药明康德市场部!或者点赞、评论、分享给其他读者吧! 相关阅读...
Science:BET结构域选择性抑制剂揭示BD1/BD2的功能差异 溴结构域和超末端结构域(Bromodomain and extraterminal domain, BET)家族蛋白是表观遗传阅读器,包括普遍表达的BRD2、BRD3、BRD4以及仅在生殖细胞表达的BRDT。 BET家族蛋白均含有高度同源的两个...
BET 属于 bromodomain 蛋白家族(溴区结构域,BRDs)中的第二类,在多种肿瘤中BET 蛋白表达上调,与细胞生长、增殖分化、凋亡坏死等多种生物学过程相关,进而参与调控肿瘤发生发展的过程。BRDs 是一类进化上高度保守的蛋白质功能结构域,能够识 别并结合组蛋白尾部的乙酰化赖氨酸残基,招募染色质调节相关蛋白、转录因子、染色...
1、组蛋白乙酰化是表观遗传研究的重要组成部分,乙酰化的组蛋白可通过dna聚合酶与rna聚合酶及转录因子作用激活基因转录。溴结构域和超末端结构域(bet)家族属于溴结构域蛋白家族(bromodomain proteins,brds),是一类进化上高度保守的蛋白,其可识别并结合组蛋白尾部的乙酰化赖氨酸残基,招募染色质调节相关蛋白、转录因子、染...
AML remains a therapeutic challenge with a high mortality rate, underscoring the need for new biologically based therapies. Somatic alterations that deregulate epigenetic programs and signal transduction pathways frequently coexist in AML. While the former class of alterations is hypothesized to promote a...
BET proteins as targets for anticancer treatment[J]. Cancer discovery, 2018, 8(1): 24-36. Shi J, Vakoc C R. The mechanisms behind the therapeutic activity of BET bromodomain inhibition[J]. Molecular cell, 2014, 54(5): 728-736. Alqahtani A, Choucair K, Ashraf M, et al. Bromodomain...
BET(bromodomain and extra-terminal)结构域家族的蛋白质是表观遗传阅读器,它们通过其溴结构域结合乙酰化组蛋白来调节基因转录。已有研究表明BET蛋白在协调正常发育,维持致癌基因表达以及对损伤和感染的生理反应所必需的转录程序中发挥重要作...
(+)-JQ1是一种BET bromodomain抑制剂,与BET bromodomain结构域的Kac位点结合,作用于BRD4(1/2),IC50值分别为77 nM和33 nM。几乎所有癌症患者中MYC都会高表达,而(+)-JQ1可以抑制MYC表达,另外,(+)-JQ1抑制细胞生长,诱导细胞周期在G1期停滞,诱导细胞凋亡,通过下调WNT表达来干扰信号通路。
图1 来源于Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development. J. Med. Chem. 2021, 64(5): 2419-2435 BET家族在人体内广泛表达,参与炎症、肥胖、肺纤维化、肿瘤等多种疾病的发生和发展过程。通过靶向抑制BET,可以诱导肿瘤细胞凋亡,从而发挥...
proteins can suppress overexpressed oncogenes, thus acting as potential antitumor agents. BET is a family of proteins with bromodomains (BRDs), which are distinguished by the presence of conserved BD1 and BD2 sequences at their N-terminals, as well as an extraterminal (ET) structure at the C...