Activity of the potent dual Abl/Src tyrosine kinase inhibitor FB2 against Bcr–Abl positive cell lines in vitro and in vivo

We have previously shown the inhibition of the small-molecule inhibitor FB2 on imatinib-sensitive and resistance CML cell lines with the wild-type Bcr–Abl fusion gene. Here we report the potent and selective antiproliferation on FB2 on transfected Ba/F3 p210 cell lines expressing various isoforms of Bcr–Abl (wild-type, Y253F, T315I). FB2 which orients Bcr–Abl and Src kinase activities, is shown to override imatinib-resistance CML involving Y253F mutation in the Abl kinase domain of the fusion protein except T315I in vivo and in vitro. Thus, we present FB2 that displays potency toward Bcr–Abl and Src as the molecular target, and which could potentially be used to override drug resistance in CML.