Systems Biology Analysis of Kinase Inhibitor Protein Target Profiles in Leukemia Treatments
To be able to understand the mechanisms of action of drugs, predict their efficacy, and anticipate their potential side-effects is important during drug development. In diseases where the genetic background of patients modulates treatment response, it might allow personalizing the therapy.
Substantial progress in proteomic technologies have made it possible to develop chemical proteomics methods, where the protein targets of a drug are affinity-purified and identified by mass spectrometry[2, 3]. Compound-protein interactions are measured in a biological context as opposed to in vitro binding assays. That is, drugprotein interactions can not only be determined proteome-wide, but also in a tissue- or cell type-dependent manner.
KeywordsChronic Myeloid Leukemia Noonan Syndrome Target Spectrum Vitro Binding Assay Human Interactome
Unable to display preview. Download preview PDF.
- 6.Rix, U., Hantschel, O., Durnberger, G., Remsing Rix, L.L., Planyavsky, M., Fernbach, N.V., Kaupe, I., Bennett, K.L., Valent, P., Colinge, J., Kocher, T., Superti-Furga, G.: Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 110, 4055–4063 (2007)CrossRefGoogle Scholar
- 8.Colinge, J., Rix, U., Superti-Furga, G.: Novel global network scores to analyze kinase inhibitor profiles. In: Chen, L., Zhang, X., Shen, B., Wu, L., Wang, Y. (eds.) 4th International Conference on Computational Systems Biology, vol. 13, pp. 305–313. World Publishing Company, Suzhou (2010)Google Scholar
- 9.Colinge, J., Rix, U., Bennett, K.L., Superti-Furga, G.: Systems biology analysis of protein-drug interactions. Proteomics Clin. Appl. (in press)Google Scholar
- 11.Gelb, B.D., Tartaglia, M.: Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Hum. Mol. Genet. 15 Spec No 2, R220-226 (2006)Google Scholar
- 12.Mullighan, C.G., Miller, C.B., Radtke, I., Phillips, L.A., Dalton, J., Ma, J., White, D., Hughes, T.P., Le Beau, M.M., Pui, C.H., Relling, M.V., Shurtleff, S.A., Downing, J.R.: BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453, 110–114 (2008)CrossRefGoogle Scholar