- Guide to PHARMACOLOGY
Synonyms: Bosulif® | SK 606 | SK-606 | SKI 606
bosutinib is an approved drug (FDA (2012), EMA (2013))
Compound class: Synthetic organic
Comment: Bosutinib is a Type-1 kinase inhibitor. This compound is a dual inhibitor of Src family kinases and Abl kinase activity .
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
View more information in the IUPHAR Pharmacology Education Project: bosutinib
|No information available.|
|Summary of Clinical Use|
|Bosutinib is approved for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. In December 2017, the FDA expanded approval to include treatment of newly-diagnosed chronic phase Ph+ CML .
Marketed formulations contain bosutinib monohydrate (PubChem CID 11990828).
|Mechanism Of Action and Pharmacodynamic Effects|
|Bosutinib targets the BCR-ABL kinase that promotes CML. In vitro studies have not been able to show bosutinib inhibition of two common imatinib-resistant BCR-ABL mutants, T315I and V299L. Bosutinib is also an inhibitor of some Src-family kinases including Src, Lyn, and Hck.|
|Peak concentration is achieved within 4-6 hours of oral administration. 96% of circulating bosutinib is bound to human plasma proteins in healthy subjects. In in vitro studies of transporter associations bosutinib is found to be a substrate and inhibitor of P-glycoprotein.|
|Bosutinib is primarily metabolized by CYP3A4, however all of the metabolites are deemed inactive.|
|91% is eliminated in feces and 3% is eliminated in urine.|
|Safety and efficacy of bosutinib have not been established in the pediatric or geriatric populations as appropriate studies have not been performed to demonstrate specific problems that would limit the usefulness of bosutinib in these populations.|
|Organ function impairment|
|In patients with pre-existing mild, moderate, and severe hepatic impairment, the daily dose of bosutinib should be reduced to 200 mg, from the 500mg daily dose recommended in patients with normal liver function. With regard to cardiac function, no significant changes in QTc were observed following a single dose of bosutinib.|
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)