Bosutinib

Bosutinib (SKI-606) is an active inhibitor of Bcr-Abl in several chronic myelogenous leukemia cell lines and transfectants. The IC50 values are in the low nanomolar range, which is 10- to 100-fold lower than those obtained with imatinib. Bosutinib has activity in cells where resistance to imatinib resulted from BCR-ABL gene amplification and in three of four Bcr-Abl point mutants examined. In in vivo experiments bosutinib retains activity in models where resistance is not caused by mutations, as well as in cells carrying the Y253F, E255K, and D276G mutations. Bosutinib binds to a different conformation of Bcr-Abl than does imatinib.