Integrating yeast chemical genomics and mammalian cell pathway analysis

Fu lai Zhou, Sheena C. Li, Yue Zhu, Wan jing Guo, Li jun Shao, Justin Nelson, Scott Simpkins, De hua Yang, Qing Liu, Yoko Yashiroda, Jin biao Xu, Yao yue Fan, Jian min Yue, Minoru Yoshida, Tian Xia, Chad L. Myers, Charles Boone, Ming wei Wang

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)1245-1255
Number of pages11
JournalActa Pharmacologica Sinica
Volume40
Issue number9
DOIs
StatePublished - Sep 1 2019

Bibliographical note

Publisher Copyright:
© 2019, CPS and SIMM.

Keywords

  • Wnt/β-catenin signaling pathway
  • autophagy
  • chemical genomics
  • tubulin cytoskeleton assembly
  • yeast

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