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

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Ericson E~Nislow C, 2008 growth (pooled culture) clozapine [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) (1S,2R)-5-methoxy-1-methyl-2-(propylamino)tetralin [200 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) sulpiride [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 3-(5-fluorouracil-1-yl)-L-alanine [200 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) (S)-(-)-sulpiride [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) (S)-alpha-methyl-4-carboxyphenylglycine [200 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 2-chloro-11-(4-methylpiperazino)dibenz[b,f]oxepin maleate [26.57 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 3'-fluorobenzylspiperone maleate [81 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Clobenztropine [65.61 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) AHN-1055 [131.22 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 4F 4PP oxalate [38.4 uM] YPD + DMSO (drug carrier control) hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 5-nonyloxytryptamine oxalate [4.56 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 6-Nitroquipazine maleate salt [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 7-chlorokynurenic acid [100 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 2-{[(2E)-3-iodoprop-2-en-1-yl](propyl)amino}tetralin-7-ol maleate [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) (1R,3S)-3-(adamantan-1-yl)-1-(aminomethyl)-3,4-dihydroisochromene-5,6-diol [100 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Altanserin [128 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) spiramide [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) amisulpride [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) bromocriptine methanesulfonate [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 1-[1-(1-benzothiophen-2-yl)cyclohexyl]piperidine maleate [200 uM] YPD + ethanol [unknown] hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) carmoxirole [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) CGP 78608 [65.6 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 4-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline dimaleate [25 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) clobenpropit dihydrobromide [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) clomipramine [30 uM] YPD hom 4,201 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Indolophenanthridine [128 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) cyproheptadine [128 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) fenoldopam [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) fluoxetine [52.43 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Fluvoxamine maleate [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Gbr 12783 [40.5 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) vanoxerine [26.572 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine [59.049 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) CHEMBL286991 [22.5 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) GR 103691 [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) GR 127935 [52.4288 uM] YPD hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) haloperidol [131.22 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) imetit dihydrobromide [50 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Indatraline [11.75 uM] YPD + DMSO (drug carrier control) hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Iodophenpropit dihydrobromide [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) CHEMBL293341 [6.26 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) L-741742 [6.25 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) LY 367385 [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) Glemanserin [200 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) BEMESETRON [200 uM] YPD + DMSO (drug carrier control) hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) metergoline [73.728 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) methiothepin maleate [200 uM] YPD hom 4,199 Quantitative
Ericson E~Nislow C, 2008 growth (pooled culture) 2-methyl-6-(phenylethynyl)pyridine [180 uM] YPD + DMSO (drug carrier control) hom 4,202 Quantitative
  • «
  • 1 (current)
  • 2
  • 3
  • 4
  • »

Curation history

Data

Oct. 4, 2016 Loaded.

Tested strains

Oct. 4, 2016 Loaded.