Modulation of alternative splicing with chemical compounds in new therapeutics for human diseases.
Modulation of alternative splicing with chemical compounds in new therapeutics for human diseases.
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在人类疾病的新疗法中用化合物调节选择性剪接。
DOI：
10.1021/cb500697f
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发表时间：
2015
影响因子：
4
通讯作者：
Hagiwara M.
中科院分区：
文献类型：
--
作者：
Ohe K;Hagiwara M.
选择性剪接是有限数量的人类基因产生复杂多样蛋白质组的关键步骤。各种疾病，包括具有“基因组密码”异常的遗传性疾病，已被发现导致与所产生的表型相关的异常错误剪接的“转录码”。基于化合物和基于核酸的策略都试图针对这种错误拼接的“转录码”。我们将简要介绍如何通过高通量筛选获得剪接修饰化合物，并概述已知的修饰剪接途径的化合物。主要的焦点将是rna结合蛋白激酶抑制剂。在正文中，我们将提到剪接修饰化合物已被深入研究的疾病，并与基于核酸的策略进行比较。关于它们参与错误剪接和非剪接事件的信息将有助于在未来的错误剪接治疗中找到更好的具有更少脱靶效应的化合物。
Alternative splicing is a critical step where a limited number of human genes generate a complex and diverse proteome. Various diseases, including inherited diseases with abnormalities in the “genome code,” have been found to result in an aberrant mis-spliced “transcript code” with correlation to the resulting phenotype. Chemical compound-based and nucleic acid-based strategies are trying to target this mis-spliced “transcript code”. We will briefly mention about how to obtain splicing-modifying-compounds by high-throughput screening and overview of what is known about compounds that modify splicing pathways. The main focus will be on RNA-binding protein kinase inhibitors. In the main text, we will refer to diseases where splicing-modifying-compounds have been intensively investigated, with comparison to nucleic acid-based strategies. The information on their involvement in mis-splicing as well as nonsplicing events will be helpful in finding better compounds with less off-target effects for future implications in mis-splicing therapy.