New Drug Approvals 2012 - Pt. XX - Bosutinib (Bosulif®)

On September 4th, the FDA approved bosutinib (marketed as Bosulif) for the treatment of patients with previously treated Philadelphia Chromosome-Positive (Ph+) Chronic Myelogenous Leukemia (CML - cancer of the white blood cells).

Chronic myelogenous leukemia is one of the four most common types of leukemia and is often associated with treatment with imatinib (CHEMBL941) as an initial therapy. However, approximately one-third of patients do not achieve an optimal response with this standard treatment. In such cases, second generation Tyrosine Kinase Inhibitors are required, but only half of the treated patients show acceptable outcomes. The patients with poor responses to either of these treatments have now the possibility to receive bosutinib (CHEMBL288441) as alternative therapy.

As suggested by the '-tinib' prefix (USAN stem), bosutinib is a protein kinase inhibitor (ATC:L01XE14). The molecule has a calculated logP of 3.88 and relative molecular weight of 530.4. It is therefore too heavy to satisfy the rule of five (maximum molecular weight of 500). The drug is taken orally with food with a recommendation of 500 mg per day. BOSULIF is available as tablet of 100 and 500 mg.

Canonical SMILES: COc1cc(Nc2c(cnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)C#N)c(Cl)cc1Cl
Standard InChI: 1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)
Standard InChI Key: UBPYILGKFZZVDX-UHFFFAOYSA-N

As the drug is metabolized by CYP3A4 (UNIPROT:P08684) it could therefore interact with other compounds acting on the enzyme, such as P-glycoprotein inhibitors or CYP3 inducers. Proton pump inhibitors can also decrease the drug concentration in the human body.

Most common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia and fatigue.

The product website is www.bosulif.com, full prescribing information is here.

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