Chemical structure of imatinib.
Western blot analysis of extracts from K562 cells, untreated (-) or treated with Imatinib (10uM for 1hr), using Phospho-Stat5 (Tyr694) (C11C5) Rabbit mAb #9359 (upper), Stat5 (D3N2B) Rabbit mAb #25656 (middle), and α-Actinin (D6F6) XP® Rabbit mAb #6487 (lower).
Imatinib is supplied as a lyophilized powder. For a 10 mM stock, reconstitute the 5 mg in 847.9 μl DMSO. Working concentrations and length of treatment can vary depending on the desired effect, but it is typically used at 1-10 μM for 1-2 hours. Soluble in DMSO at 100 mg/ml; poorly soluble in ethanol. Soluble in water at 200 mg/ml.
Store lyophilized or in solution at -20ºC, desiccated. Protect from light. In lyophilized form, the chemical is stable for 24 months. Once in solution, use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.
C29H31N7O + CH4SO3
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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