Small-molecule inhibitors of the Myc oncoprotein.
Small-molecule inhibitors of the Myc oncoprotein.
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DOI：
10.1016/j.bbagrm.2014.03.005
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发表时间：
2015-05
影响因子：
4.7
通讯作者：
Prochownik, Edward V.
中科院分区：
文献类型：
--
作者：
Fletcher, Steven;Prochownik, Edward V.
c-Myc（Myc）癌蛋白是最有吸引力的癌症靶点之一，因为其在大多数肿瘤中被解除调节，并且其抑制深刻地影响它们的生长和/或存活。然而，其作为很少突变的转录因子的作用、其缺乏酶活性（可针对其制备合适的药物抑制剂）以及其由正常细胞表达在很大程度上是其被视为“不可用药”的原因。然而，过去几年的工作已经开始扭转这一观点，使我们能够在全球基因调控的更大背景下看待Myc。因此，Myc和它的专性异二聚体伙伴，最大，是不可或缺的协调招聘和翻译后修饰的核心转录机制的组成部分。此外，Myc的过度表达重新编程了许多关键的细胞功能，并改变了细胞对其抑制的敏感性。因此，这一新知识已成为开发新药物方法的框架。这些包括继续开发直接作用于抑制关键Myc-Max相互作用的小分子，间接作用于阻止启动生产性转录所必需的Myc指导的翻译后修饰的小分子，以及抑制Myc转化细胞特别依赖的重要途径的小分子。
The c-Myc (Myc) oncoprotein is among the most attractive of cancer targets given that is deregulated in the majority of tumors and that its inhibition profoundly affects their growth and/or survival. However, its role as a seldom-mutated transcription factor, its lack of enzymatic activity for which suitable pharmaceutical inhibitors could be crafted and its expression by normal cells have largely been responsible for its being viewed as “undruggable”. Work over the past several years, however, has begun to reverse this idea by allowing us to view Myc within the larger context of global gene regulatory control. Thus, Myc and its obligate heterodimeric partner, Max, are integral to the coordinated recruitment and post-translational modification of components of the core transcriptional machinery. Moreover, Myc over-expression re-programs numerous critical cellular functions and alters the cell’s susceptibility to their inhibition. This new knowledge has therefore served as a framework upon which to develop new pharmaceutical approaches. These include the continuing development of small molecules which act directly to inhibit the critical Myc-Max interaction, those which act indirectly to prevent Myc-directed post-translational modifications necessary to initiate productive transcription and those which inhibit vital pathways upon which the Myc-transformed cell is particularly reliant.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.4161/cc.9.9.11346
发表时间：
2010-05
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Cho S;Schroeder S;Ott M
通讯作者：
Ott M
影响因子：
11.4
作者：
Chng, W-J;Huang, G. F.;Chung, T. H.;Ng, S. B.;Gonzalez-Paz, N.;Troska-Price, T.;Mulligan, G.;Chesi, M.;Bergsagel, P. L.;Fonseca, R.
通讯作者：
Fonseca, R.
DOI：
10.1124/jpet.110.170555
发表时间：
2010-12-01
影响因子：
3.5
作者：
Clausen, Dana M.;Guo, Jianxia;Eiseman, Julie L.
通讯作者：
Eiseman, Julie L.
影响因子：
20.3
作者：
Chen, I. Ming;Harvey, Richard C.;Willman, Cheryl L.
通讯作者：
Willman, Cheryl L.