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High-Throughput Screening: today's biochemical and cell-based approaches.
Drug Discovery Today ( IF 7.4 ) Pub Date : 2020-08-12 , DOI: 10.1016/j.drudis.2020.07.024
Vincent Blay 1 , Bhairavi Tolani 2 , Sunita P Ho 1 , Michelle R Arkin 3
Affiliation  

High-throughput screening (HTS) provides starting chemical matter in the adventure of developing a new drug. In this review, we survey several HTS methods used today for hit identification, organized in two main flavors: biochemical and cell-based assays. Biochemical assays discussed include fluorescence polarization and anisotropy, FRET, TR-FRET, and fluorescence lifetime analysis. Binding-based methods are also surveyed, including NMR, SPR, mass spectrometry, and DSF. On the other hand, cell-based assays discussed include viability, reporter gene, second messenger, and high-throughput microscopy assays. We devote some emphasis to high-content screening, which is becoming very popular. An advisable stage after hit discovery using phenotypic screens is target deconvolution, and we provide an overview of current chemical proteomics, in silico, and chemical genetics tools. Emphasis is made on recent CRISPR/dCas-based screens. Lastly, we illustrate some of the considerations that inform the choice of HTS methods and point to some areas with potential interest for future research.



中文翻译:

高通量筛选:当今的生化和基于细胞的方法。

高通量筛选 (HTS) 为开发新药的冒险提供了起始化学物质。在这篇综述中,我们调查了目前用于命中识别的几种 HTS 方法,主要分为两种类型:生化和基于细胞的分析。讨论的生化分析包括荧光偏振和各向异性、FRET、TR-FRET 和荧光寿命分析。还研究了基于结合的方法,包括 NMR、SPR、质谱和 DSF。另一方面,所讨论的基于细胞的检测包括活力、报告基因、第二信使和高通量显微镜检测。我们将重点放在高内容筛选上,这正变得非常流行。使用表型筛选发现命中后的一个可取的阶段是目标反卷积,我们提供了当前化学蛋白质组学的概述,in silico和化学遗传学工具。重点是最近基于 CRISPR/dCas 的屏幕。最后,我们说明了选择 HTS 方法的一些考虑因素,并指出了一些对未来研究具有潜在兴趣的领域。

更新日期:2020-08-12
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