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整合RNA干扰和小分子筛选以鉴定药物开发靶点

Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.

作者信息

Drosopoulos Konstantinos, Linardopoulos Spiros

机构信息

The Breast Cancer Toby Robins Research Centre, The Institute of Cancer Research, London, UK.

Cancer Research UK, Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK.

出版信息

Methods Mol Biol. 2019;1953:33-42. doi: 10.1007/978-1-4939-9145-7_3.

DOI:10.1007/978-1-4939-9145-7_3
PMID:30912014
Abstract

Cellular models for siRNA and small molecule high-throughput screening have been widely used in the last decade to identify targets for drug discovery. As an example, we present a twofold readout approach based on cell viability and multipolar phenotype. To maximize the discovery of potential targets and at the same time reduce the number of false positives in our dataset, we have combined focused and rationally designed custom siRNA libraries with small molecule inhibitor libraries. Here we describe a cellular model for centrosome amplification as an example of how to design and perform a multiple readout/multiple screening strategy.

摘要

在过去十年中,用于小干扰RNA(siRNA)和小分子高通量筛选的细胞模型已被广泛用于识别药物研发的靶点。例如,我们提出了一种基于细胞活力和多极表型的双重读数方法。为了最大程度地发现潜在靶点,同时减少数据集中的假阳性数量,我们将针对性设计的定制siRNA文库与小分子抑制剂文库结合起来。在这里,我们以中心体扩增的细胞模型为例,描述如何设计和实施多重读数/多重筛选策略。

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