Imatinib and nilotinib, but not dasatinib, inhibit the oxidoreductase activity of NQO2. (A) Enzymatic quinone reduction underlying the activation of mitomycin C that was used to determine inhibition of NQO2. (B) NQO2 oxidoreductase inhibition assays for imatinib (■/—), nilotinib (▴/----), and dasatinib (▾/…) using the anticancer agent mitomycin C as a substrate and NADH as a cosubstrate. The graph shows the mean and standard deviation of 3 independent experiments. (C) Crystal structure of dimeric NQO2 in complex with menadione (blue sticks) and FAD (yellow sticks) (PDB entry 2QR2). The close-up view of the active site (bottom) shows a possible model for binding of imatinib (green sticks) to NQO2 and competition with the cosubstrate FAD. The figure was generated with Pymol (http://pymol.sourceforge.net/, DeLano Scientific).