IC50: 314 nmol/L (Csk, Src family protein tyrosine kinases); IC50: 2.4 nmol/L(Abl kinase).
Bosutinib (drate) is an oral Src/Abl tyrosine kinase inhibito with IC50 of 1.2 nM and 1 nM, respectively[1].
Bosutinib (drate) is an active inhibitor of Bcr-Abl in several chronic myelogenous leukemia cell lines, with IC50 values in the low nanomolar range[2].
Cell Proliferation Assay[2]
| Cell Line: | The leukemic Bcr-Abl+ cell lines (KCL22, K562, KU812, and Lama84) |
| Concentration: | 0.1 μmol/L |
| Incubation Time: | 72 h |
| Result: | Inhibited several human CML derived cell lines with IC50 values ranging from 1 to 20 nmol/L. |
Bosutinib (drate) (oral gavage; 75 mg/kg twice daily or 150 mg/kg once daily) has activity against human KU812 xenografts in nude mice. Bosutinib (drate) (150 mg/kg; once daily, 5 days weekly) has activity against syngeneic Bcr-Abl WT and mutant Ba/F3 xenografts[2].
| Animal Model: | KU812CM L xenograft model[2] |
| Dosage: | 75 mg/kg twice daily or 150 mg/kg once daily |
| Administration: | Bosutinib (oral gavage; 75 mg/kg twice daily or 150 mg/kg once daily) |
| Result: | Had the therapeutic activity and produced a dose- and schedule-dependent weight loss. |
| Animal Model: | Syngeneic Bcr-Abl WT and mutant Ba/F3 xenografts[2] |
| Dosage: | 150 mg/kg |
| Administration: | Bosutinib (150 mg/kg; once daily, 5 days weekly) |
| Result: | Decreased the rate of tumor growth and prolonged event-free survival of mice. |
[1]. Jorge E Cortes, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol. 2012 Oct 1;30(28):3486-92.
[2]. Miriam Puttini, et al. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res. 2006 Dec 1;66(23):11314-22.