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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4055-4063. Prepublished online as a Blood First Edition Paper on August 24, 2007; DOI 10.1182/blood-2007-07-102061. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-07-102061v1 110/12/4055    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rix, U. Articles by Superti-Furga, G. Search for Related Content PubMed PubMed Citation Articles by Rix, U. Articles by Superti-Furga, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 19, 2007 Accepted August 23, 2007 Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib reveal novel kinase and non-kinase targets Uwe Rix, Oliver Hantschel, Gerhard Durnberger, Lily L Remsing Rix, Melanie Planyavsky, Nora V Fernbach, Ines Kaupe, Keiryn L Bennett, Peter Valent, Jacques Colinge, Thomas Kocher, and Giulio Superti-Furga* Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM), Vienna, Austria Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria * Corresponding author; email: gsuperti{at}cemm.oeaw.ac.at. The BCR-ABL tyrosine kinase inhibitor imatinib represents the current frontline therapy in chronic myeloid leukemia. Since many patients develop imatinib resistance, two second-generation drugs, nilotinib and dasatinib, displaying increased potency against BCR-ABL were developed. To predict potential side effects and novel medical uses we generated comprehensive drug-protein interaction profiles by chemical proteomics for all three drugs. Our studies yielded four major findings: i. The interaction profiles of the three drugs displayed strong differences and only a small overlap covering the ABL kinases. ii. Dasatinib bound in excess of thirty Tyr- and Ser-/Thr-kinases, including major regulators of the immune system suggesting that dasatinib might have a particular impact on immune function. iii. Despite the high specificity of nilotinib the receptor tyrosine kinase DDR1 was identified and validated as an additional major target. iv. The oxidoreductase NQO2 was bound and inhibited by imatinib and nilotinib at physiologically relevant drug concentrations representing the first non-kinase target of these drugs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. A. Byers, B. Sen, B. Saigal, L. Diao, J. Wang, M. Nanjundan, T. Cascone, G. B. Mills, J. V. Heymach, and F. M. Johnson Reciprocal Regulation of c-Src and STAT3 in Non-Small Cell Lung Cancer Clin. Cancer Res., November 15, 2009; 15(22): 6852 - 6861. [Abstract] [Full Text] [PDF] J. L. Snead, T. O'Hare, L. T. Adrian, C. A. Eide, T. Lange, B. J. Druker, and M. W. Deininger Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis Blood, October 15, 2009; 114(16): 3459 - 3463. [Abstract] [Full Text] [PDF] G. Suo, Y. Jiang, B. Cowan, and J. Y.J. 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