Bafetinib

Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM and 19 nM, respectively. Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells, respectively. Bafetinib (0.2 mg/kg/day) significantly inhibits tumor growth, and completely inhibits tumor growth without adverse effects at 20 mg/kg/day in Bcr-Abl-positive KU812 mouse model. Bafetinib (NS-187) inhibited both Tyr393-phosphorylated and Tyr393-unphosphorylated Abl, resulting in significant in vitro growth inhibition of cells expressing six of seven mutated Bcr-Abl kinases, though not T315I. Furthermore, Bafetinib (INNO-406) prolonged the survival of mice injected with leukemic cells expressing all mutated Bcr-Abl tested except T315I, and its efficacy correlated well with its in vitro effects. INNO-406 (formerly NS-187) is 25 to 55 times more potent than imatinib mesylate in vitro and at least 10 times more potent in vivo. Bafetinib is currently in Phase II clinical trials in patients with hormone refractory prostate cancer.