{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:30:45Z","timestamp":1772782245639,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2012,9,30]],"date-time":"2012-09-30T00:00:00Z","timestamp":1348963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Chem Biol"],"published-print":{"date-parts":[[2012,11]]},"DOI":"10.1038\/nchembio.1085","type":"journal-article","created":{"date-parts":[[2012,9,30]],"date-time":"2012-09-30T18:04:28Z","timestamp":1349028268000},"page":"905-912","source":"Crossref","is-referenced-by-count":91,"title":["Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML"],"prefix":"10.1038","volume":"8","author":[{"given":"Georg E","family":"Winter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Rix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karoline V","family":"Gleixner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Grebien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Gridling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 C","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian P","family":"Breitwieser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bilban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Colinge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Valent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiryn L","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Forest M","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Superti-Furga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,9,30]]},"reference":[{"key":"BFnchembio1085_CR1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nrc1300","volume":"4","author":"H Kitano","year":"2004","unstructured":"Kitano, H. Cancer as a robust system: implications for anticancer therapy. Nat. Rev. Cancer 4, 227\u2013235 (2004).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnchembio1085_CR2","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/nbt.1549","volume":"27","author":"J Leh\u00e1r","year":"2009","unstructured":"Leh\u00e1r, J. et al. Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat. Biotechnol. 27, 659\u2013666 (2009).","journal-title":"Nat. Biotechnol."},{"key":"BFnchembio1085_CR3","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","volume":"313","author":"J Lamb","year":"2006","unstructured":"Lamb, J. et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313, 1929\u20131935 (2006).","journal-title":"Science"},{"key":"BFnchembio1085_CR4","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/nchembio.216","volume":"5","author":"U Rix","year":"2009","unstructured":"Rix, U. & Superti-Furga, G. Target profiling of small molecules by chemical proteomics. Nat. Chem. Biol. 5, 616\u2013624 (2009).","journal-title":"Nat. Chem. Biol."},{"key":"BFnchembio1085_CR5","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1074\/mcp.M900285-MCP200","volume":"8","author":"C Pan","year":"2009","unstructured":"Pan, C., Olsen, J.V., Daub, H. & Mann, M. Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol. Cell. Proteomics 8, 2796\u20132808 (2009).","journal-title":"Mol. Cell. Proteomics"},{"key":"BFnchembio1085_CR6","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nchembio.118","volume":"4","author":"AL Hopkins","year":"2008","unstructured":"Hopkins, A.L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 4, 682\u2013690 (2008).","journal-title":"Nat. Chem. Biol."},{"key":"BFnchembio1085_CR7","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/nrc2787","volume":"10","author":"ZA Knight","year":"2010","unstructured":"Knight, Z.A., Lin, H. & Shokat, K.M. Targeting the cancer kinome through polypharmacology. Nat. Rev. Cancer 10, 130\u2013137 (2010).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnchembio1085_CR8","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1182\/blood-2008-03-144790","volume":"113","author":"A Quint\u00e1s-Cardama","year":"2009","unstructured":"Quint\u00e1s-Cardama, A. & Cortes, J. Molecular biology of BCR-ABL1\u2013positive chronic myeloid leukemia. Blood 113, 1619\u20131630 (2009).","journal-title":"Blood"},{"key":"BFnchembio1085_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0065-230X(04)91001-9","volume":"91","author":"BJ Druker","year":"2004","unstructured":"Druker, B.J. Imatinib as a paradigm of targeted therapies. Adv. Cancer Res. 91, 1\u201330 (2004).","journal-title":"Adv. Cancer Res."},{"key":"BFnchembio1085_CR10","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1126\/science.1062538","volume":"293","author":"ME Gorre","year":"2001","unstructured":"Gorre, M.E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876\u2013880 (2001).","journal-title":"Science"},{"key":"BFnchembio1085_CR11","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1158\/0008-5472.CAN-03-1484","volume":"64","author":"NJ Donato","year":"2004","unstructured":"Donato, N.J. et al. Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia. Cancer Res. 64, 672\u2013677 (2004); erratum 64, 2306 (2004).","journal-title":"Cancer Res."},{"key":"BFnchembio1085_CR12","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1182\/blood.V96.3.1070","volume":"96","author":"FX Mahon","year":"2000","unstructured":"Mahon, F.X. et al. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 96, 1070\u20131079 (2000).","journal-title":"Blood"},{"key":"BFnchembio1085_CR13","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/nrc2559","volume":"9","author":"J Zhang","year":"2009","unstructured":"Zhang, J., Yang, P.L. & Gray, N.S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 9, 28\u201339 (2009).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnchembio1085_CR14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/leu.2010.238","volume":"25","author":"D Bixby","year":"2011","unstructured":"Bixby, D. & Talpaz, M. Seeking the causes and solutions to imatinib-resistance in chronic myeloid leukemia. Leukemia 25, 7\u201322 (2011).","journal-title":"Leukemia"},{"key":"BFnchembio1085_CR15","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ccr.2009.09.028","volume":"16","author":"T O\u2032Hare","year":"2009","unstructured":"O\u2032Hare, T. et al. AP24534, a pan\u2013BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16, 401\u2013412 (2009).","journal-title":"Cancer Cell"},{"key":"BFnchembio1085_CR16","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1158\/0008-5472.CAN-10-3224","volume":"71","author":"CA Eide","year":"2011","unstructured":"Eide, C.A. et al. The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile. Cancer Res. 71, 3189\u20133195 (2011).","journal-title":"Cancer Res."},{"key":"BFnchembio1085_CR17","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.cell.2011.08.046","volume":"147","author":"F Grebien","year":"2011","unstructured":"Grebien, F. et al. Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis. Cell 147, 306\u2013319 (2011).","journal-title":"Cell"},{"key":"BFnchembio1085_CR18","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.ccr.2011.11.004","volume":"20","author":"LM Packer","year":"2011","unstructured":"Packer, L.M. et al. Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia. Cancer Cell 20, 715\u2013727 (2011).","journal-title":"Cancer Cell"},{"key":"BFnchembio1085_CR19","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/j.1744-7348.1939.tb06990.x","volume":"26","author":"CI Bliss","year":"1939","unstructured":"Bliss, C.I. The toxicity of poisons applied jointly. Ann. Appl. Biol. 26, 585\u2013615 (1939).","journal-title":"Ann. Appl. Biol."},{"key":"BFnchembio1085_CR20","doi-asserted-by":"publisher","first-page":"7977","DOI":"10.1073\/pnas.1337088100","volume":"100","author":"AA Borisy","year":"2003","unstructured":"Borisy, A.A. et al. Systematic discovery of multicomponent therapeutics. Proc. Natl. Acad. Sci. USA 100, 7977\u20137982 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio1085_CR21","doi-asserted-by":"publisher","first-page":"2758","DOI":"10.1021\/pr1012784","volume":"10","author":"FP Breitwieser","year":"2011","unstructured":"Breitwieser, F.P. et al. General statistical modeling of data from protein relative expression isobaric tags. J. Proteome Res. 10, 2758\u20132766 (2011).","journal-title":"J. Proteome Res."},{"key":"BFnchembio1085_CR22","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1074\/mcp.M400129-MCP200","volume":"3","author":"PL Ross","year":"2004","unstructured":"Ross, P.L. et al. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol. Cell. Proteomics 3, 1154\u20131169 (2004).","journal-title":"Mol. Cell. Proteomics"},{"key":"BFnchembio1085_CR23","doi-asserted-by":"publisher","first-page":"P3","DOI":"10.1186\/gb-2003-4-5-p3","volume":"4","author":"G Dennis Jr.","year":"2003","unstructured":"Dennis, G. Jr. et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 4, P3 (2003).","journal-title":"Genome Biol."},{"key":"BFnchembio1085_CR24","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.cell.2008.04.043","volume":"133","author":"X Chen","year":"2008","unstructured":"Chen, X. et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106\u20131117 (2008).","journal-title":"Cell"},{"key":"BFnchembio1085_CR25","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio1085_CR26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1093\/nar\/29.2.397","volume":"29","author":"M Schuhmacher","year":"2001","unstructured":"Schuhmacher, M. et al. The transcriptional program of a human B cell line in response to Myc. Nucleic Acids Res. 29, 397\u2013406 (2001).","journal-title":"Nucleic Acids Res."},{"key":"BFnchembio1085_CR27","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1007\/PL00006139","volume":"44","author":"J Dopazo","year":"1997","unstructured":"Dopazo, J. & Carazo, J.M. Phylogenetic reconstruction using an unsupervised growing neural network that adopts the topology of a phylogenetic tree. J. Mol. Evol. 44, 226\u2013233 (1997).","journal-title":"J. Mol. Evol."},{"key":"BFnchembio1085_CR28","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1073\/pnas.90.8.3216","volume":"90","author":"S Gupta","year":"1993","unstructured":"Gupta, S., Seth, A. & Davis, R.J. Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62. Proc. Natl. Acad. Sci. USA 90, 3216\u20133220 (1993).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio1085_CR29","doi-asserted-by":"crossref","first-page":"23521","DOI":"10.1016\/S0021-9258(18)54312-X","volume":"266","author":"A Seth","year":"1991","unstructured":"Seth, A., Alvarez, E., Gupta, S. & Davis, R.J. A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression. J. Biol. Chem. 266, 23521\u201323524 (1991).","journal-title":"J. Biol. Chem."},{"key":"BFnchembio1085_CR30","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.semcancer.2006.08.004","volume":"16","author":"SR Hann","year":"2006","unstructured":"Hann, S.R. Role of post-translational modifications in regulating c-Myc proteolysis, transcriptional activity and biological function. Semin. Cancer Biol. 16, 288\u2013302 (2006).","journal-title":"Semin. Cancer Biol."},{"key":"BFnchembio1085_CR31","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.molcel.2006.01.009","volume":"21","author":"B Benassi","year":"2006","unstructured":"Benassi, B. et al. c-Myc phosphorylation is required for cellular response to oxidative stress. Mol. Cell 21, 509\u2013519 (2006).","journal-title":"Mol. Cell"},{"key":"BFnchembio1085_CR32","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/j.cell.2011.08.017","volume":"146","author":"JE Delmore","year":"2011","unstructured":"Delmore, J.E. et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146, 904\u2013917 (2011).","journal-title":"Cell"},{"key":"BFnchembio1085_CR33","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1038\/nature09504","volume":"468","author":"P Filippakopoulos","year":"2010","unstructured":"Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067\u20131073 (2010).","journal-title":"Nature"},{"key":"BFnchembio1085_CR34","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nchembio.775","volume":"8","author":"O Hantschel","year":"2012","unstructured":"Hantschel, O. et al. BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. Nat. Chem. Biol. 8, 285\u2013293 (2012).","journal-title":"Nat. Chem. Biol."},{"key":"BFnchembio1085_CR35","doi-asserted-by":"publisher","first-page":"6082","DOI":"10.1128\/MCB.02202-05","volume":"26","author":"IJ Griswold","year":"2006","unstructured":"Griswold, I.J. et al. Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib. Mol. Cell. Biol. 26, 6082\u20136093 (2006).","journal-title":"Mol. Cell. Biol."},{"key":"BFnchembio1085_CR36","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/nsmb.1486","volume":"15","author":"M Azam","year":"2008","unstructured":"Azam, M., Seeliger, M.A., Gray, N.S., Kuriyan, J. & Daley, G.Q. Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat. Struct. Mol. Biol. 15, 1109\u20131118 (2008).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFnchembio1085_CR37","doi-asserted-by":"publisher","first-page":"4567","DOI":"10.1182\/blood-2011-05-355594","volume":"118","author":"JE Cortes","year":"2011","unstructured":"Cortes, J.E. et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 118, 4567\u20134576 (2011).","journal-title":"Blood"},{"key":"BFnchembio1085_CR38","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/nrc904","volume":"2","author":"S Pelengaris","year":"2002","unstructured":"Pelengaris, S., Khan, M. & Evan, G. c-MYC: more than just a matter of life and death. Nat. Rev. Cancer 2, 764\u2013776 (2002).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnchembio1085_CR39","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/0092-8674(92)90241-4","volume":"70","author":"CL Sawyers","year":"1992","unstructured":"Sawyers, C.L., Callahan, W. & Witte, O.N. Dominant negative MYC blocks transformation by ABL oncogenes. Cell 70, 901\u2013910 (1992).","journal-title":"Cell"},{"key":"BFnchembio1085_CR40","doi-asserted-by":"publisher","first-page":"20380","DOI":"10.1073\/pnas.0810485105","volume":"105","author":"B Luo","year":"2008","unstructured":"Luo, B. et al. Highly parallel identification of essential genes in cancer cells. Proc. Natl. Acad. Sci. USA 105, 20380\u201320385 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio1085_CR41","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1158\/1541-7786.MCR-10-0356","volume":"9","author":"M Albajar","year":"2011","unstructured":"Albajar, M. et al. MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib. Mol. Cancer Res. 9, 564\u2013576 (2011).","journal-title":"Mol. Cancer Res."},{"key":"BFnchembio1085_CR42","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nrm1703","volume":"6","author":"S Adhikary","year":"2005","unstructured":"Adhikary, S. & Eilers, M. Transcriptional regulation and transformation by Myc proteins. Nat. Rev. Mol. Cell Biol. 6, 635\u2013645 (2005).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFnchembio1085_CR43","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1038\/nrc2231","volume":"8","author":"N Meyer","year":"2008","unstructured":"Meyer, N. & Penn, L.Z. Reflecting on 25 years with MYC. Nat. Rev. Cancer 8, 976\u2013990 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnchembio1085_CR44","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/nchembio.462","volume":"6","author":"B Palsson","year":"2010","unstructured":"Palsson, B. & Zengler, K. The challenges of integrating multi-omic data sets. Nat. Chem. Biol. 6, 787\u2013789 (2010).","journal-title":"Nat. Chem. Biol."},{"key":"BFnchembio1085_CR45","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/leu.2009.228","volume":"24","author":"U Rix","year":"2010","unstructured":"Rix, U. et al. A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells. Leukemia 24, 44\u201350 (2010).","journal-title":"Leukemia"}],"container-title":["Nature Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nchembio.1085.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nchembio.1085","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nchembio.1085.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T19:31:17Z","timestamp":1684438277000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nchembio.1085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,30]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["BFnchembio1085"],"URL":"https:\/\/doi.org\/10.1038\/nchembio.1085","relation":{},"ISSN":["1552-4450","1552-4469"],"issn-type":[{"value":"1552-4450","type":"print"},{"value":"1552-4469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,30]]}}}