Ericson E~Nislow C, 2008

Pubmed ID 18688276
Title Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast.
Authors Elke Ericson, Marinella Gebbia, Lawrence E Heisler, Jan Wildenhain, Mike Tyers, Guri Giaever, Corey Nislow
Abstract To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.
Citation PLoS Genet. 2008; 4:e1000151

Datasets

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Papers Phenotype Conditions Collection Tested mutants Data Details
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) clozapine [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) (+)-AJ 76 hydrochloride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) (RS)-(+/-)-Sulpiride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) (S)-(-)-5-fluorowillardiine [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) (S)-(-)-sulpiride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) (S)-MCPG [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 2-Chloro-11-(4-methylpiperazino)dibenz[b,f]oxepin maleate [26.57 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 3'-Fluorobenzylspiperone maleate [81 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 3a-[(4-Chlorophenyl)phenylmethoxy] tropane hydrochloride [65.61 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 3a-Bis-(4-fluorophenyl) methoxytropane hydrochloride [131.22 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 4F 4PP [38.4 uM] hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 5-Nonyloxytryptamine oxalate [4.56 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 6-nitroquipazine maleate [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 7-chlorokynurenic acid [100 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) 7-Hydroxy-PIPAT maleate [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) A 77636 hydrochloride [100 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Altanserin hydrochloride [128 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) AMI-193 [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Amisulpride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) BRL 15572 hydrochloride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Bromocriptine mesylate [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) BTCP [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Carmoxirole hydrochloride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) CGP 78608 hydrochloride [65.6 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) CGS 12066B dimaleate [25 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Clobenpropit dihydrobromide [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) clomipramine [30 uM] hom 4,201 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) CY 208-243 [128 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) cyproheptadine [128 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Fenoldopam hydrochloride [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) fluoxetine [52.43 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Fluvoxamine maleate [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) GBR 12783 dihydrochloride [40.5 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) GBR 12909 dihydrochloride [26.572 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) GBR 12935 dihydrochloride [59.049 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) GBR 13069 dihydrochloride [22.5 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) GR 103691 [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) GR 127935 hydrochloride [52.4288 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Haloperidol [131.22 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Imetit dihydrobromide [50 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) indatraline [11.75 uM] hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Iodophenpropit dihydrobromide [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) L-741,741 hydrochloride [6.26 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) L741,742 hydrochloride [6.25 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) LY 367385 [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) MDL 11,939 [200 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) MDL 72222 [200 uM] hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Metergoline [73.728 uM] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) Methiothepin maleate [200 uM] hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (relative abundance in pooled culture) MPEP hydrochloride [180 uM] hom 4,202 Quantitative
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Curation history

Oct. 4, 2016 Tested strains loaded.
Oct. 4, 2016 Data loaded.