Targeting Transcription Factors for Cancer Treatment.
Targeting Transcription Factors for Cancer Treatment.
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DOI：
10.3390/molecules23061479
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发表时间：
2018-06-19
期刊：
影响因子：
--
通讯作者：
David-Cordonnier MH
中科院分区：
文献类型：
--
作者：
Lambert M;Jambon S;Depauw S;David-Cordonnier MH
转录因子参与了大量的人类疾病，如癌症，它们占迄今为止鉴定的所有癌基因的约20%。长期以来，除了配体诱导的核受体外，转录因子被认为是“不可治疗”的靶点。这些转录因子在结构、功能（表达、降解、与辅因子和其他蛋白质的相互作用）以及它们与DNA结合模式的动态方面的进步知识改变了这一假设，并为靶向转录因子的新疗法铺平了道路。在这里，我们讨论了在癌症模型中靶向转录因子的各种方法：通过调节它们的表达或降解，通过阻断蛋白质/蛋白质相互作用，通过靶向转录因子本身以防止其通过结合口袋或在DNA相互作用位点的DNA结合，这些抑制剂中的一些目前正在使用或评估用于癌症治疗。小分子对转录因子的这种不同靶向通过现代化学来促进，现代化学开发了各种各样的被设计为特异性中止转录因子的原始分子，并且通过使用新技术来增加对它们的病理学意义的了解，以便使改善转录因子致癌功能的治疗控制成为可能。
Transcription factors are involved in a large number of human diseases such as cancers for which they account for about 20% of all oncogenes identified so far. For long time, with the exception of ligand-inducible nuclear receptors, transcription factors were considered as “undruggable” targets. Advances knowledge of these transcription factors, in terms of structure, function (expression, degradation, interaction with co-factors and other proteins) and the dynamics of their mode of binding to DNA has changed this postulate and paved the way for new therapies targeted against transcription factors. Here, we discuss various ways to target transcription factors in cancer models: by modulating their expression or degradation, by blocking protein/protein interactions, by targeting the transcription factor itself to prevent its DNA binding either through a binding pocket or at the DNA-interacting site, some of these inhibitors being currently used or evaluated for cancer treatment. Such different targeting of transcription factors by small molecules is facilitated by modern chemistry developing a wide variety of original molecules designed to specifically abort transcription factor and by an increased knowledge of their pathological implication through the use of new technologies in order to make it possible to improve therapeutic control of transcription factor oncogenic functions.
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DOI：
10.1073/pnas.93.24.13623
发表时间：
1996-11-26
影响因子：
11.1
作者：
Bailly, C;Payet, D;Waring, MJ
通讯作者：
Waring, MJ
影响因子：
14.9
作者：
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通讯作者：
Ciccarelli FD
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Bulyk ML
影响因子：
3.9
作者：
Bashkin, James K.;Aston, Karl;Ramos, Joseph P.;Koeller, Kevin J.;Nanjunda, Rupesh;He, Gaofei;Dupureur, Cynthia M.;Wilson, W. David
通讯作者：
Wilson, W. David
影响因子：
20.3
作者：
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通讯作者：
Mueller，Beatrice U.