Wang Jixia, Zhang Xiuli, Fang Ye, Liang Xinmiao
Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, New York 14831, USA.
Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
Curr Pharm Des. 2016;22(21):3190-200. doi: 10.2174/1381612822666160224142048.
Most drugs exert their biological and physiological effects via binding to protein targets. Although drugs are traditionally optimized against a single protein, most marketed drugs exhibit clinically relevant polypharmacology - the activity of drugs at multiple targets. The wide-spread presence of polypharmacology makes it challenging to assess the mechanisms of action of multi-target drugs.
This paper first reviews approaches for discovering multi-targets of drug molecules, then discusses key characteristics of label-free cell phenotypic assays, and finally focuses on how to use these assays to assess drug polypharmacology.
labelfree cell phenotypic assays have ability to provide a holistic view of drug action in living cells with wide phenotype/ target/pathway coverage, and permit effective deconvolution of the action of multi-target drugs at the whole cell level.
Label-free cell phenotypic assays hold great potential in assessing drug polypharmacology.
大多数药物通过与蛋白质靶点结合发挥其生物学和生理学效应。尽管传统上药物是针对单一蛋白质进行优化的，但大多数上市药物都表现出临床相关的多药理学特性——药物在多个靶点的活性。多药理学的广泛存在使得评估多靶点药物的作用机制具有挑战性。
本文首先综述了发现药物分子多靶点的方法，然后讨论了无标记细胞表型分析的关键特征，最后重点介绍了如何使用这些分析来评估药物多药理学。
无标记细胞表型分析能够在活细胞中提供药物作用的整体视图，具有广泛的表型/靶点/途径覆盖范围，并允许在全细胞水平上有效解卷积多靶点药物的作用。
无标记细胞表型分析在评估药物多药理学方面具有巨大潜力。
