1. Integrating yeast chemical genomics and mammalian cell pathway analysis.
- Author
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Zhou FL, Li SC, Zhu Y, Guo WJ, Shao LJ, Nelson J, Simpkins S, Yang DH, Liu Q, Yashiroda Y, Xu JB, Fan YY, Yue JM, Yoshida M, Xia T, Myers CL, Boone C, and Wang MW
- Subjects
- Correlation of Data, Genetic Profile, Genomics methods, HEK293 Cells, HeLa Cells, Humans, Proof of Concept Study, beta Catenin metabolism, Autophagy drug effects, Drug Discovery, Saccharomyces cerevisiae drug effects, Small Molecule Libraries pharmacology, Wnt Signaling Pathway drug effects
- Abstract
Chemical genomics has been applied extensively to evaluate small molecules that modulate biological processes in Saccharomyces cerevisiae. Here, we use yeast as a surrogate system for studying compounds that are active against metazoan targets. Large-scale chemical-genetic profiling of thousands of synthetic and natural compounds from the Chinese National Compound Library identified those with high-confidence bioprocess target predictions. To discover compounds that have the potential to function like therapeutic agents with known targets, we also analyzed a reference library of approved drugs. Previously uncharacterized compounds with chemical-genetic profiles resembling existing drugs that modulate autophagy and Wnt/β-catenin signal transduction were further examined in mammalian cells, and new modulators with specific modes of action were validated. This analysis exploits yeast as a general platform for predicting compound bioactivity in mammalian cells.
- Published
- 2019
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