Development of a High-Content Screening Assay Panel to Accelerate Mechanism of Action Studies for Oncology Research

Development of a High-Content Screening Assay Panel to Accelerate Mechanism of Action Studies for Oncology Research
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开发高内涵筛选检测试剂盒以加速肿瘤学研究的行动研究机制

DOI:
10.1177/1087057112450050
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发表时间:
2012
影响因子:
--
通讯作者:
Vivek Abraham
Vivek Abraham
中科院分区:
化学3区
文献类型:
--
作者:
D. Towne;Emily Nicholl;K. Comess;S. Galasinski;P. Hajduk;Vivek Abraham

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Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth–inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas.
一种可扩展的高内涵细胞毒性测定,对线粒体代谢活性的变化不敏感。
DOI: 10.3727/096504003773994842
发表时间: 2004
期刊: Oncology research
影响因子: 3.1
作者:
Vogt,Andreas;Kalb,EricaN;Lazo,JohnS
通讯作者: Lazo,JohnS