Inhibition of NQO2 by Abl kinase inhibitors. A) Chemical structures of the Abl kinase inhibitors imatinib, nilotinib, and dasatinib. Imatinib consists of a pyridine ring (A, green), an aminopyrimidine ring (B, blue), a methylbenzene ring (C, red), a benzamide ring (D, magenta), and a N-methylpiperazine ring (E, orange). The structurally analogous rings of nilotinib and dasatinib are similarly labeled. B) NQO2 inhibition assays for kinase inhibitors imatinib (black circles), nilotinib (blue squares), dasatinib (green diamonds), and the flavonoid NQO2 inhibitor quercetin (magenta triangles). The data were fit to the concentration-response equation , where x is the log of the inhibitor concentration, to yield IC50 values of 42 nM, 82 nM, and 381 nM for quercetin, imatinib, and nilotinib, respectively. Dasatinib was a very poor inhibitor, with an IC50 value > 100 μM.
Winger et al. BMC Structural Biology 2009 9:7 doi:10.1186/1472-6807-9-7