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.
Original language | English (US) |
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Pages (from-to) | 1245-1255 |
Number of pages | 11 |
Journal | Acta Pharmacologica Sinica |
Volume | 40 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2019 |
Bibliographical note
Publisher Copyright:© 2019, CPS and SIMM.
Keywords
- Wnt/β-catenin signaling pathway
- autophagy
- chemical genomics
- tubulin cytoskeleton assembly
- yeast