| Description |
Imatinib is a tyrosine kinase (TK) inhibitor that is a relatively specific ATP-binding site antagonist of Bcr-Abl, PDGF receptor, and c-Kit TKs (1-3). Results are encouraging in chronic myeloid leukemia (CML) clinical trials and imatinib has become a paradigm for targeted cancer therapeutics (4-6). Signal transduction through phospho-tyrosine pathways has been studied extensively, and tyrosine phosphorylation has been linked to multiple cell growth and differentiation pathways (7-9). Because the observed leukemic state of CML is dependent on the intact Bcr-Abl tyrosine kinase activity, extensive work has been done to identify substrates of Bcr-Abl and thus possible mechanisms leading to a myeloid expansion. Many groups have characterized prominent tyrosine-phosphorylated protein substrates in both CML blasts and Bcr-Abl-expressing cell lines, including SHIP, c-Cbl, Dok, Shc, and CrkL (10-15). In addition, key signal transduction pathways involving PI3 kinase, Ras, Myc, and Stat5 are also activated in a Bcr-Abl kinase-dependent manner (16).
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Western blot analysis of extracts from K-562 cells, untreated (-) or treated with imatinib (10 μM, 1 hr; +), using PathScan ® Bcr/Abl Activity Assay: Phospho-c-Abl, Phospho-Stat5 and Phospho-CrkL Multiplex Western Detection Cocktail #5300 to detect inhibition of phospho-Bcr-Abl, phospho-Stat5, and phospho-CrkL.
Chemical structure of imatinib.