| Literature DB >> 31138898 |
Fu-Lai Zhou1,2, Sheena C Li3, Yue Zhu1,2, Wan-Jing Guo1,2, Li-Jun Shao1,2, Justin Nelson4, Scott Simpkins4, De-Hua Yang1, Qing Liu1, Yoko Yashiroda3, Jin-Biao Xu5, Yao-Yue Fan5, Jian-Min Yue5, Minoru Yoshida3,6,7, Tian Xia8, Chad L Myers9, Charles Boone10,11, Ming-Wei Wang12,13.
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.Entities:
Keywords: Wnt/β-catenin signaling pathway; autophagy; chemical genomics; tubulin cytoskeleton assembly; yeast
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Year: 2019 PMID: 31138898 PMCID: PMC6786357 DOI: 10.1038/s41401-019-0231-y
Source DB: PubMed Journal: Acta Pharmacol Sin ISSN: 1671-4083 Impact factor: 6.150