Fig. 6

The isolated effects of the two competition mechanisms when ATP level varies. Determined by removing the binding of TKIs to the NBD and to the substrate site for nilotinib (left), imatinib (middle), and dasatinib (right). Initial concentrations of paclitaxel, P-gp, and TKI were 3 μM, 10 μM, and 1 μM, respectively. ATP concentrations were varied from 1 μM to 10 mM. The solid lines correspond to simulations where the TKI can bind to both P-gp binding sites, the dotted line corresponds to simulations where the TKI can only bind to the NBD, and the dashed line corresponds to simulations where the TKI can only bind to the substrate binding site