Bosutinib (Bos)

Bosutinib is a tyrosine kinase inhibitor undergoing research for use in the treatment of cancer. Bosutinib only has two known absolute contraindications, which are: known hypersensitivity to bosutinib and liver impairment. Bosutinib is both a substrate and an inhibitor of P-glycoprotein (P-gp) and CYP3A4. Hence P-gp and CYP3A4 inhibitors may increase plasma levels of bosutinib. Likewise CYP3A4 inducers may reduce plasma concentrations of bosutinib. It may also alter the metabolism and uptake of other drugs that are substrates for P-gp and CYP3A4. Animal studies using up to three-times the clinical exposure to bosutinib have failed to demonstrate any carcinogenic effects. Mutagenic and clastogenic effects were not detected in vitro. Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines, but did not inhibit T315I and V299L mutant cells.