In vitro
SKI-606 (bosutinib) is a potent, orally bioavailable, dual Src/Abl kinase inhibitor. SKI-606 can inhibit cellular Src kinase activity in intact tumor cells with IC50 of 250 nM. Besides inhibiting Src kinase, SKI-606 can also inhibit the phosphorylation of focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2), and Crk-associated substrate (p130Cas). SKI-606 can reduce cell motility and invasion of breast cancer cell lines with an IC50 of approximately 250 nM. But SKI-606 do not influence cell proliferation and survival at this concentration.
In vivo
SKI-606 (bosutinib) has antiproliferative effects in chronic myelogenous leukemia cells, to inhibit colon tumor cell colony formation in soft agar, and to suppress tumor growth in K562 and colon tumor cell xenograft models. SKI-606 (Bosutinib) blocks prostate cancer invasion, growth, and metastasis in vitro and in vivo. Treating with SKI-606, there is a reduction in the phosphorylation of Akt, MAPK and focal adhesion kinase. Besides the inhibition to kinases, SKI-606 can decrease the level of the expression of tumor progression-associated genes uPAR, MMP-2, MMP-9, N-cadherin, fibronectin, BMP-2 (bone morphogenetic protein 2), BMP-6 (bone morphogenetic protein 6), IL-8 (interleukin 8), and TGF-beta (transforming growth factor beta) in prostate cancer cells.
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