Lum PY~Shoemaker DD, 2004

Pubmed ID 14718172
Title Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.
Authors Pek Yee Lum, Christopher D Armour, Sergey B Stepaniants, Guy Cavet, Maria K Wolf, J Scott Butler, Jerald C Hinshaw, Philippe Garnier, Glenn D Prestwich, Amy Leonardson, Philip Garrett-Engele, Christopher M Rush, Martin Bard, Greg Schimmack, John W Phillips, Christopher J Roberts, Daniel D Shoemaker
Abstract Modern medicine faces the challenge of developing safer and more effective therapies to treat human diseases. Many drugs currently in use were discovered without knowledge of their underlying molecular mechanisms. Understanding their biological targets and modes of action will be essential to design improved second-generation compounds. Here, we describe the use of a genome-wide pool of tagged heterozygotes to assess the cellular effects of 78 compounds in Saccharomyces cerevisiae. Specifically, lanosterol synthase in the sterol biosynthetic pathway was identified as a target of the antianginal drug molsidomine, which may explain its cholesterol-lowering effects. Further, the rRNA processing exosome was identified as a potential target of the cell growth inhibitor 5-fluorouracil. This genome-wide screen validated previously characterized targets or helped identify potentially new modes of action for over half of the compounds tested, providing proof of this principle for analyzing the modes of action of clinically relevant compounds.
Citation Cell 2004; 116:121-37

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) flucytosine [200 ng/mL] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) 5-fluoro-2'-deoxyuridine [300 uM] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) 5-fluorouracil [2 uM] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) actinomycin D [20 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) amitriptyline [125 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) amphotericin B [600 ng/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) cytarabine [500 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) asulam [250 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) atenolol [4 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) zidovudine [2 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) oxybuprocaine [900 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) caffeine [700 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) camptothecin [100 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) carbendazim [100 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) chlorpromazine [37.5 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) cisplatin [600 uM] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) clomipramine [50 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) clotrimazole [37.5 ng/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) cycloheximide [10 ng/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) cymoxanil [1.25 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) daunorubicin [40 ng/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) desipramine [200 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) diltiazem [2 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) dimethyl sulfoxide [2.5%] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) doxorubicin [3 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) doxycycline [400 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) dyclonine [32 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) efavirenz [300 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) Erythromycin ethylsuccinate [2.5 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) ethanol [1.25%] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) fenpropimorph [0.00001%] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) flurbiprofen [75 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) gemfibrozil [30 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) gliotoxin [3 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) haloperidol [62.5 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) histamine [3 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) hydroxyurea [20 mM] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) ibuprofen [10 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) imipramine [312.5 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) indometacin [100 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) isoniazide [275 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) kanamycin [6 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) lovastatin [40 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) menadione [40 ng/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) methotrexate [12.5 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) methyl methanesulfonate [0.002%] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) metoclopramide [7 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) Molsidomine [2 mg/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) nalidixic acid [325 ug/ml] SC het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) naproxen [40 ug/ml] SC het 3,503 Quantitative only for hits
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Curation history

Data

Oct. 14, 2014 To request.
April 4, 2016 Request sent.
April 5, 2016 Request sent.
Aug. 16, 2016 Request sent.
Aug. 16, 2016 Request abandoned.
Aug. 16, 2016 Ready to load.
Sept. 5, 2016 Loaded.

Tested strains

Oct. 14, 2014 Ready to load.
Sept. 5, 2016 Loaded.