bafetinib   

GtoPdb Ligand ID: 7906

Synonyms: INNO-406 | Lyn-IN-1 | NS-187
Compound class: Synthetic organic
Comment: Bafetinib is a second-generation, dual Lyn/Abl kinase inhibitor [1,6] with therapeutic.potential for the treatment of imatinib-resistant or -intolerant B-cell chronic lymphocytic leukemia (CLL), and prostate cancer. Data indicate that bafetinib crosses the blood-brain-barrier, reaching therapeutic concentration, so the drug's potential for treatment of brain tumours is also under investigation.

Note that we have mapped the chemical structure using the updated CAS registry number stipulated in INN proposed list 101 (2009) to the CID specified here, but the name maps to four other CIDs in PubChem.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 99.17
Molecular weight 576.26
XLogP 3.32
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CN(C1CCN(C1)Cc1ccc(cc1C(F)(F)F)C(=O)Nc1ccc(c(c1)Nc1nccc(n1)c1cncnc1)C)C
Isomeric SMILES CN([C@H]1CCN(C1)Cc1ccc(cc1C(F)(F)F)C(=O)Nc1ccc(c(c1)Nc1nccc(n1)c1cncnc1)C)C
InChI InChI=1S/C30H31F3N8O/c1-19-4-7-23(13-27(19)39-29-36-10-8-26(38-29)22-14-34-18-35-15-22)37-28(42)20-5-6-21(25(12-20)30(31,32)33)16-41-11-9-24(17-41)40(2)3/h4-8,10,12-15,18,24H,9,11,16-17H2,1-3H3,(H,37,42)(H,36,38,39)/t24-/m0/s1
InChI Key ZGBAJMQHJDFTQJ-DEOSSOPVSA-N
No information available.
Summary of Clinical Use
Bafetinib has been assessed in two completed Phase II clinical trials for hormone-refractory prostate cancer (NCT01215799) and relapsed or refractory B-cell chronic lymphocytic leukemia (CLL; NCT01144260).
Both the US FDA and EMA have granted bafetinib orphan drug status for the treatment of Philadelphia chromosome-positive CML.
Mechanism Of Action and Pharmacodynamic Effects
Bafetinib specifically binds to and inhibits the Bcr/Abl fusion protein tyrosine kinase, an abnormal enzyme produced by Philadelphia chromosomal translocation associated with chronic myeloid leukemia (CML) [5]. It also inhibits the Src-family member Lyn tyrosine kinase, upregulated in imatinib-resistant CML cells and in a variety of solid cancer cell types [4]. The inhibitory effect of bafetinib on these kinases may decrease cellular proliferation and induce apoptosis in tumor cells driven by their overexpression [2].