Bosutinib

BCR-ABL Inhibitor
DB06616
Approved Indication

Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy in adult patients.

10 Targets
5 Resistance Mutations
2 References
3UE4 Structure Loaded
3D Structure PDB: 3UE4
Switch structure: RCSB ↗
Mechanism of Action

Bosutinib is a tyrosine kinase inhibitor. Although it is able to inhibit several tyrosine kinases such as Src, Lyn, and Hck, which are members of the Src-family of kinases, its primary target is the Bcr-Abl kinase. The Bcr-Abl gene is a chimeric oncogene created from the fusion of the breakpoint-cluster (Bcr) gene and Abelson (Abl) tyrosine gene. This chromosomal abnormality results in the formation of what is commonly known as the Philadelphia chromosome or Philadelphia translocation. The Bcr-Abl gene expresses a particular kinase that promotes the progression of CML. A decrease in the growth and size of the CML tumour has been observed following administration of bosutinib. Bosutinib did not inhibit the T315I and V299L mutant cells.

Resistance Mutations — 7 resistance samples observed in COSMIC
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ABL1
p.F359I p.F378I p.L248R p.L267R p.V299L

Resistance mutations sourced from COSMIC Drug Resistance database. Cyan = on-target · Amber = off-target · numbered badge = PubMed references for that mutation

Details
DrugBank ID DB06616 ↗
Approval Date 2012-09-04
Molecular Weight 530.446 g/mol
Drug Class BCR-ABL Inhibitor
ATC Codes L01XE14
Synonyms Bosulif®, Bosutinib, Bosutinib Monohydrate
SMILES
COC1=CC(NC2=C(C=NC3=CC(OCCCN4CCN(C)CC4)=C(OC)C=C23)C#N)=C(Cl)C=C1Cl
ADMET Profile
Computing properties…
Drug References (DrugBank)