{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T03:33:19Z","timestamp":1777347199028,"version":"3.51.4"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2009,9,18]],"date-time":"2009-09-18T00:00:00Z","timestamp":1253232000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000512","type":"journal-article","created":{"date-parts":[[2009,9,18]],"date-time":"2009-09-18T00:28:49Z","timestamp":1253233729000},"page":"e1000512","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Transcriptional Profiling of the Dose Response: A More Powerful Approach for Characterizing Drug Activities"],"prefix":"10.1371","volume":"5","author":[{"given":"Rui-Ru","family":"Ji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heshani","family":"de Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yisheng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Bruccoleri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiqing","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul S.","family":"Kayne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac M.","family":"Neuhaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl-Heinz","family":"Ott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Becky","family":"Penhallow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark I.","family":"Cockett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan O.","family":"Siemers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Ross-Macdonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2009,9,18]]},"reference":[{"key":"ref1","article-title":"Dritte defensione, von der Beischreibung der neuen Rezepte. Sieben Defensiones, Verantwortung \u00fcber etliche Verunglimpfungen seiner Mi\u00dfg\u00f6nner","author":"Paracelsus","year":"1564"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/nbt1239","article-title":"The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.","volume":"24","author":"L Shi","year":"2006","journal-title":"Nat Biotechnol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/ng1305","article-title":"Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.","volume":"36","author":"K Stegmaier","year":"2004","journal-title":"Nat Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1124\/mol.104.010165","article-title":"Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors.","volume":"67","author":"RA Parker","year":"2005","journal-title":"Mol Pharmacol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1471-4159.2006.03750.x","article-title":"Effects of antidepressant treatment on gene expression profile in mouse brain: cell type-specific transcription profiling using laser microdissection and microarray analysis.","volume":"97","author":"C Boehm","year":"2006","journal-title":"J Neurochem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1177\/1087057106289808","article-title":"Development of a screening assay for surrogate markers of CHK1 inhibitor-induced cell cycle release.","volume":"11","author":"CP Fanton","year":"2006","journal-title":"J Biomol Screen"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrd2155","article-title":"Why is cancer drug discovery so difficult?","volume":"6","author":"A Kamb","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"R255","DOI":"10.1186\/gb-2007-8-11-r255","article-title":"Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer: rationale for patient selection and efficacy monitoring.","volume":"8","author":"XD Wang","year":"2007","journal-title":"Genome Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"11473","DOI":"10.1073\/pnas.0604348103","article-title":"Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries.","volume":"103","author":"J Inglese","year":"2006","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e126","DOI":"10.1093\/nar\/gnh119","article-title":"Multiplex mRNA assay using electrophoretic tags for high-throughput gene expression analysis.","volume":"32","author":"H Tian","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jplph.2005.04.015","article-title":"Comparative quantification of pharmacodynamic parameters of chiral compounds (RRR- vs. all-rac-alpha tocopherol) by global gene expression profiling.","volume":"162","author":"PY Muller","year":"2005","journal-title":"J Plant Physiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/1471-2407-5-125","article-title":"Combining RNA interference and kinase inhibitors against cell signalling components involved in cancer.","volume":"5","author":"M O'Grady","year":"2005","journal-title":"BMC Cancer"},{"key":"ref13","article-title":"Handbook of the Logistic Distribution:","year":"1991"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00280-006-0325-3","article-title":"Platinum drug effects on the expression of genes in the polyamine pathway: time-course and concentration-effect analysis based on Affymetrix gene expression profiling of A2780 ovarian carcinoma cells.","volume":"59","author":"R Varma","year":"2007","journal-title":"Cancer Chemother Pharmacol"},{"key":"ref15","first-page":"43","article-title":"Simultaneous modeling of concentration-effect and time-course patterns in gene expression data from microarrays.","volume":"5","author":"YF Brun","year":"2008","journal-title":"Cancer Genomics Proteomics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1098\/rspb.1983.0093","article-title":"Operational models of pharmacological agonism.","volume":"220","author":"JW Black","year":"1983","journal-title":"Proc R Soc Lond B Biol Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nrc2044","article-title":"The Connectivity Map: a new tool for biomedical research.","volume":"7","author":"J Lamb","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nbt1068","article-title":"A small molecule-kinase interaction map for clinical kinase inhibitors.","volume":"23","author":"MA Fabian","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nrd2324","article-title":"Flying under the radar: the new wave of BCR-ABL inhibitors.","volume":"6","author":"A Quintas-Cardama","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"6658","DOI":"10.1021\/jm049486a","article-title":"Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src\/Abl kinase inhibitor with potent antitumor activity in preclinical assays.","volume":"47","author":"LJ Lombardo","year":"2004","journal-title":"J Med Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nbt1358","article-title":"A quantitative analysis of kinase inhibitor selectivity.","volume":"26","author":"MW Karaman","year":"2008","journal-title":"Nat Biotechnol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.2174\/156802607781696837","article-title":"Recent advances of MEK inhibitors and their clinical progress.","volume":"7","author":"JY Wang","year":"2007","journal-title":"Curr Top Med Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1182\/blood-2007-07-102061","article-title":"Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib reveal novel kinase and non-kinase targets.","author":"U Rix","year":"2007","journal-title":"Blood:"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1021\/bi061893w","article-title":"Thermodynamics of Nucleotide and Non-ATP-Competitive Inhibitor Binding to MEK1 by Circular Dichroism and Isothermal Titration Calorimetry.","volume":"46","author":"CK Smith","year":"2007","journal-title":"Biochemistry"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1096\/fj.07-105627","article-title":"Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis.","volume":"22","author":"A Akhmetshina","year":"2008","journal-title":"FASEB J"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s00280-006-0323-5","article-title":"Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration.","volume":"59","author":"A Brown","year":"2007","journal-title":"Cancer Chemotherapy and Pharmacology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"6188","DOI":"10.1038\/sj.onc.1204834","article-title":"Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation.","volume":"20","author":"S Xie","year":"2001","journal-title":"Oncogene"},{"key":"ref28","article-title":"Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol.","volume":"2","author":"L Lam","year":"2001","journal-title":"Genome Biology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1137\/0111030","article-title":"An Algorithm for Least-Squares Estimation of Nonlinear Parameters.","volume":"11","author":"DW Marquardt","year":"1963","journal-title":"SIAM Journal on Applied Mathematics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1093\/bioinformatics\/bti565","article-title":"Ontological analysis of gene expression data: current tools, limitations, and open problems.","volume":"21","author":"P Khatri","year":"2005","journal-title":"Bioinformatics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkm882","article-title":"KEGG for linking genomes to life and the environment.","volume":"36","author":"M Kanehisa","year":"2008","journal-title":"Nucl Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nature04304","article-title":"BRAF mutation predicts sensitivity to MEK inhibition.","volume":"439","author":"DB Solit","year":"2006","journal-title":"Nature"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1038\/sj.onc.1203481","article-title":"Serine phosphorylation of STATs.","volume":"19","author":"T Decker","year":"2000","journal-title":"Oncogene"},{"key":"ref35","first-page":"407","article-title":"The interferon signaling network and transcription factor C\/EBP-beta.","volume":"4","author":"H Li","year":"2007","journal-title":"Cell Mol Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nrd2070","article-title":"Targeting signal transduction as a strategy to treat inflammatory diseases.","volume":"5","author":"LA O'Neill","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrd2289","article-title":"Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses.","volume":"6","author":"KL Jeffrey","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1358\/dnp.2005.18.4.908658","article-title":"JAK\/STAT-dependent gene regulation by cytokines.","volume":"18","author":"D Hebenstreit","year":"2005","journal-title":"Drug News Perspect"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.4049\/jimmunol.178.5.2623","article-title":"The JAK-STAT signaling pathway: input and output integration.","volume":"178","author":"PJ Murray","year":"2007","journal-title":"J Immunol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1186\/1471-2164-8-455","article-title":"Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells.","volume":"8","author":"Y Xu","year":"2007","journal-title":"BMC Genomics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/nbt1328","article-title":"Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors.","volume":"25","author":"M Bantscheff","year":"2007","journal-title":"Nat Biotechnol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1158\/1541-7786.MCR-08-0169","article-title":"Inhibition of Src Family Kinases with Dasatinib Blocks Migration and Invasion of Human Melanoma Cells.","volume":"6","author":"R Buettner","year":"2008","journal-title":"Mol Cancer Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2337\/db08-0080","article-title":"Imatinib Mesylate Reduces Endoplasmic Reticulum Stress and Induces Remission of Diabetes in db\/db Mice.","volume":"58","author":"MS Han","year":"2009","journal-title":"Diabetes"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1182\/blood-2006-07-036012","article-title":"Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia.","volume":"109","author":"S Picard","year":"2007","journal-title":"Blood"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/nm1446","article-title":"Cardiotoxicity of the cancer therapeutic agent imatinib mesylate.","volume":"12","author":"R Kerkela","year":"2006","journal-title":"Nat Med"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1038\/sj.onc.1204252","article-title":"Regulation of the G2\/M transition by p53.","volume":"20","author":"WR Taylor","year":"2001","journal-title":"Oncogene"},{"key":"ref47","first-page":"565","article-title":"A statistically precise and relatively simple method of estimating the bio-assay with quantal response, based upon the logistic function.","volume":"48","author":"J Berkson","year":"1953","journal-title":"Journal of the American Statistical Association"},{"key":"ref48","first-page":"417","article-title":"The Application of Transcriptional Profiling in Model Connectivity and Lead Assessment in Drug Discovery.","author":"M Neubauer","year":"2007"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"7180","DOI":"10.1158\/1078-0432.CCR-06-1112","article-title":"Dasatinib (BMS-354825) Pharmacokinetics and Pharmacodynamic Biomarkers in Animal Models Predict Optimal Clinical Exposure.","volume":"12","author":"FR Luo","year":"2006","journal-title":"Clin Cancer Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa055104","article-title":"Nilotinib in Imatinib-Resistant CML and Philadelphia Chromosome-Positive ALL.","volume":"354","author":"H Kantarjian","year":"2006","journal-title":"N Engl J Med"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2210-4-11","article-title":"A homotropic two-state model and auto-antagonism.","volume":"4","author":"N Bindslev","year":"2004","journal-title":"BMC Pharmacol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0092-8674(00)00015-5","article-title":"Functional discovery via a compendium of expression profiles.","volume":"102","author":"TR Hughes","year":"2000","journal-title":"Cell"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/nar\/gng015","article-title":"Summaries of Affymetrix GeneChip probe level data.","volume":"31","author":"RA Irizarry","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/biomet\/73.3.751","article-title":"An improved Bonferroni procedure for multiple tests of significance.","volume":"73","author":"RJ Simes","year":"1986","journal-title":"Biometrika"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: a Practical and Powerful Approach to Multiple Testing.","volume":"57","author":"Y Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society B"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1214\/ss\/1177011454","article-title":"A Survey of Exact Inference for Contingency Tables.","volume":"7","author":"A Agresti","year":"1992","journal-title":"Statist Sci"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:14:29Z","timestamp":1739344469000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000512"}},"subtitle":[],"editor":[{"given":"Greg","family":"Tucker-Kellogg","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2009,9,18]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2009,9,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000512","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,18]]}}}