Cell-Based Kinetic Target-Guided Synthesis of an Enzyme Inhibitor,ACS Medicinal Chemistry Letters

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Cell-Based Kinetic Target-Guided Synthesis of an Enzyme Inhibitor
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2018-03-08 00:00:00 , DOI: 10.1021/acsmedchemlett.7b00535
Henrik Antti ₁ , Magnus Sellstedt ₁

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Finding a new drug candidate for a selected target is an expensive and time-consuming process. Target guided-synthesis, or in situ click chemistry, is a concept where the drug target is used to template the formation of its own inhibitors from reactive building blocks. This could simplify the identification of drug candidates. However, with the exception of one example of an RNA-target, target-guided synthesis has always employed purified targets. This limits the number of targets that can be screened by the method. By applying methods from the field of metabolomics, we demonstrate that target-guided synthesis with protein targets also can be performed directly in cell-based systems. These methods offer new possibilities to conduct screening for drug candidates of difficult protein targets in cellular environments.

中文翻译：

酶抑制剂的基于细胞的动力学指导合成

为选定的目标物寻找新的候选药物是一个昂贵且耗时的过程。目标引导合成或原位点击化学是一种概念，其中药物靶标用于模板化由反应性构建基团自身形成的抑制剂。这样可以简化候选药物的识别。然而，除了RNA靶标的一个实例以外，靶标指导的合成一直采用纯化的靶标。这限制了该方法可以筛选的目标数量。通过应用代谢组学领域的方法，我们证明了具有蛋白质靶标的靶标指导的合成也可以直接在基于细胞的系统中进行。这些方法提供了在细胞环境中筛选困难蛋白靶标候选药物的新可能性。

更新日期：2018-03-08

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