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| Trade names | Bosulif |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Protein binding | 94–96% |
| Metabolism | ByCYP3A4, to inactive metabolites |
| Eliminationhalf-life | 22.5±1.7 hours |
| Excretion | Fecal (91.3%) and kidney (3%) |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.149.122 |
| Chemical and physical data | |
| Formula | C26H29Cl2N5O3 |
| Molar mass | 530.45 g·mol−1 |
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Bosutinib, sold under the brand nameBosulif, is a small moleculeBCR-ABL andsrctyrosine kinase inhibitor used for the treatment ofchronic myelogenous leukemia.[2]
Originally synthesized byWyeth, it is being developed byPfizer.[citation needed]
It is an ATP-competitiveBcr-Abl tyrosine-kinase inhibitor with an additional inhibitory effect onSrc family kinases (including Src, Lyn and Hck).[3][4] It has also shown activity against the receptors forplatelet derived growth factor andvascular endothelial growth factor.[5] 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.[3]
Bosutinib is metabolized through CYP3A4.
Bosutinib received USFDA and EUEuropean Medicines Agency approval in September 2012, and March 2013, respectively for the treatment of adults withPhiladelphia chromosome-positive (Ph+)chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.[6][7][8][9]
Bosutinib has two known absolute contraindications, which are: known hypersensitivity to bosutinib and liver impairment.[10][11]
Bosutinib is both a substrate and an inhibitor ofP-glycoprotein (P-gp) andCYP3A4.[3] Hence P-gp and CYP3A4 inhibitors may increase plasma levels of bosutinib.[3] Likewise CYP3A4 inducers may reduce plasma concentrations of bosutinib.[3] It may also alter the metabolism and uptake (into the GIT by means of its P-gp inhibitory effects) of other drugs that are substrates for P-gp and CYP3A4.[3]
