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
Papers Phenotype Conditions Collection Tested mutants Data Details
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) 5-fluoro-cytosine [200 ng/mL], minimal complete [standard] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) floxuridine [300 uM], minimal complete [standard] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], 5-fluoro-uracil [2 uM] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) actinomycin D [20 ug/ml], minimal complete [standard] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], amitriptyline [125 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], amphotericin B [600 ng/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], arabinofuranosyl cytidine [500 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], asulam [250 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], atenolol [4 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], zidovudine [2 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], benoxinate [900 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], caffeine [700 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], camptothecin [100 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], carbendazim [100 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], chlorpromazine [37.5 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) cisplatin [600 uM], minimal complete [standard] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], clomipramine [50 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], clotrimazole [37.5 ng/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], cycloheximide [10 ng/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], cymoxanil [1.25 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], daunomycin [40 ng/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], desipramine [200 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], diltiazem [2 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], dymethyl sulfoxide [2.5%] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], doxorubicin [3 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], doxycycline [400 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], dyclonine [32 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], efavirenz [300 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], erythromycin ethylsuccinate [2.5 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], ethanol [1.25%] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], fenpropimorph [0.00001%] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], flurbiprofen [75 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], gemfibrozil [30 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], gliotoxin [3 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], Haloperidol [62.5 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], histamine [3 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], hydroxyurea [20 mM] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], ibuprofen [10 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], imipramine [312.5 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], indomethacin [100 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], isoniazid [275 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], kanamycin [6 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], lovastatin [40 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], menadione [40 ng/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], methotrexate [12.5 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], methylmethane sulphonate [0.002%] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], metoclopramide [7 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], molsidomine [2 mg/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], nalidixic acid [325 ug/ml] het 3,503 Quantitative only for hits
Lum PY~Shoemaker DD, 2004 growth (relative abundance in pooled culture) minimal complete [standard], naproxen [40 ug/ml] het 3,503 Quantitative only for hits
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Curation history

Oct. 14, 2014 Tested strains to load.
Oct. 14, 2014 Data to request.
April 4, 2016 Data requested.
April 5, 2016 Data requested.
Aug. 16, 2016 Data requested.
Aug. 16, 2016 Data abandoned.
Aug. 16, 2016 Data to load.
Sept. 5, 2016 Tested strains loaded.
Sept. 5, 2016 Data loaded.