bosutinib

Ligand id: 5710

Name: bosutinib

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Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 82.88
Molecular weight 529.16
XLogP 2.57
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

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.
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.
Pharmacokinetics
Absorption/Distribution
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.
Biotransformation/Metabolism
Bosutinib is primarily metabolized by CYP3A4, however all of the metabolites are deemed inactive.
Elimination
91% is eliminated in feces and 3% is eliminated in urine.
Population pharmacokinetics
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.
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