Journal
CHEMISTRY & BIOLOGY
Volume 18, Issue 10, Pages 1273-1283Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2011.07.018
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Funding
- NHGRI
- CIHR [MOPS-84305, MOPS-81340, MOP-97904, MOP-68813]
- Canadian Cancer Society [020380]
- NSERC [RGPIN 356873-08]
- Marie Curie fellowship
- Canada Research Chair (CRC) in Chemical Genetics
- CRC in Molecular Neurobiology
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Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened similar to 81,000 compounds in Saccharomyces cerevisiae and identified similar to 7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the similar to 7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided.
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