Bafetinib (NS-187, INNO-406) is an orally-available, ATP-competitive inhibitor of Bcr-Abl and Lyn with IC50 values of 11 and 26 nM, respectively. Structurally similar to imatinib, Bafetinib possesses 10- to 50-fold greater biochemical potency as well as in cell proliferation assays (11 nM and 22 nM in K562 cells and 293T cells, respectively). [1] In a number of point-mutated Abl kinase domains, with the exception of T315I, Bafetinib inhibited phosphorylation much more potently than did imatinib.

Bafetinib inhibits the kinase activity of both phosphorylated and unphosphorylated Tyr393 forms of Abl with IC50 values of 72 and 30 nM, respecitively. [1] Though Bafetinib is a pGP substrate, residual concentrations are sufficient for anti-leukemic activity and is further aided by treatment with cyclosporin A. [2]

Bafetinib has been shown to induce cell death in Bcr-Abl leukemia cell lines by both caspase-mediated and caspase-independent mechanisms. In vivo, this cell death is independent of the activity status of caspase. [3]