Bosutinib
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| Trade names | Bosulif |
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Oral |
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| Pharmacokinetic data | |
| Protein binding | 94–96% |
| Metabolism | By CYP3A4, to inactive metabolites |
| Biological half-life | 22.5±1.7 hours |
| Excretion | Foecal (91.3%) and renal (3%) |
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| ECHA InfoCard | 100.149.122 |
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| Formula | C26H29Cl2N5O3 |
| Molar mass | 530.446 g/mol |
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Bosutinib (rINN/USAN; codenamed SKI-606, marketed under the trade name Bosulif) is a tyrosine kinase inhibitor undergoing research for use in the treatment of cancer. Originally synthesized by Wyeth, it is being developed by Pfizer.
Bosutinib received US FDA and EU European Medicines Agency approval on September 4, 2012 and 27 March 2013 respectively for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.
Adverse effects by incidence:
Very common (>10% frequency):
Common (1-10% frequency):
Uncommon (0.1-1% frequency):
Bosutinib 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 (into the GIT by means of its P-gp inhibitory effects) of other drugs that are substrates for P-gp and CYP3A4.
Animal studies using up to three-times the clinical exposure (in terms of AUC) to bosutinib have failed to demonstrate any carcinogenic effects. Mutagenic and clastogenic effects were not detected in vitro.
It is an ATP-competitive Bcr-Abl tyrosine-kinase inhibitor with an additional inhibitory effect on SRc family kinases (including Src, Lyn and Hck). 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.
Some commercial stocks of bosutinib (from sources other than the Pfizer material used for clinical trials) have recently been found to have the incorrect chemical structure, calling the biological results obtained with them into doubt.
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