Bromodomains as therapeutic targets in cancer
Bromodomains as therapeutic targets in cancer
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DOI：
10.1093/bfgp/elt007
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发表时间：
2013-05-01
影响因子：
4
通讯作者：
Dawson, Mark A.
中科院分区：
文献类型：
--
作者：
Barbieri, Isaia;Cannizzaro, Ester;Dawson, Mark A.
表观基因组的可塑性长期以来被认为是治疗干预的独特机会。对靶向表观遗传机制组分以获得治疗效果的兴趣最初是针对染色质修饰酶。然而，药物化学的进步现在使得利用染色质界面的蛋白质-蛋白质相互作用成为可能。溴结构域（Bromodomains，BRD）是一个保守的基序，被许多染色质相关蛋白用来识别和结合乙酰化组蛋白尾部。对溴结构域和额外末端蛋白家族（BRD 2、BRD 3、BRD 4和BRDT）具有高特异性的小分子最近已显示在各种恶性肿瘤中具有显著的临床前功效。这些发现为探索其他BRD蛋白作为癌症治疗的新靶点提供了动力。
The malleability of the epigenome has long been recognized as a unique opportunity for therapeutic intervention. Interest in targeting components of the epigenetic machinery for therapeutic gain had initially been aimed at chromatin modifying enzymes. However, advances in medicinal chemistry have now made it possible to exploit protein-protein interactions at the chromatin interface. Bromodomains (BRD) are a conserved motif used by a large number of chromatin-associated proteins to recognize and bind acetylated histone tails. Small molecules with high specificity for the Bromodomain and Extra Terminal family of proteins (BRD2, BRD3, BRD4 and BRDT) have recently been shown to have remarkable pre-clinical efficacy in various malignancies. These findings have provided the impetus for exploring other BRD proteins as novel targets in cancer therapy.