期刊
CELL CHEMICAL BIOLOGY
卷 23, 期 1, 页码 3-9出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2015.11.008
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NIGMS NIH HHS [R01 GM038627] Funding Source: Medline
The enthusiasm for phenotypic screening as an approach for small-molecule discovery has increased dramatically over the last several years. The recent increase in phenotype-based discoveries is in part due to advancements in phenotypic readouts in improved disease models that recapitulate clinically relevant biology in cell culture. Of course, a major historical barrier to using phenotypic assays in chemical biology has been the challenge in determining the mechanism of action (MoA) for compounds of interest. With the combination of medically inspired phenotypic screening and the development of modern MoA methods, we can now start implementing this approach in chemical probe and drug discovery. In this Perspective, we highlight recent advances in phenotypic readouts and MoA determination by discussing several case studies in which both activities were required for understanding the chemical biology involved and, in some cases, advancing toward clinical development.
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