Fig. 7

The isolated effects of the two competition mechanisms when P-gp 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, ATP, and TKI were 3 μM, 3 mM, and 1 μM, respectively. P-gp concentrations were varied from 0 to 100 μM. The solid lines correspond to simulations where the TKI can bind to both P-gp NBD and SBD, 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 SBD