fig2

Figure 2. Hypothetical model demonstrating the different possible interactions of TKIs with ABC transporters. (A) The competitive binding of TKI at the drug binding site and hereby preventing the binding of the drug and consequently its efflux; (B) the situation when TKI is not a substrate of ABC transporter, but it binds at the NBD or other site inducing allosteric modulation of the transporter which leads to its inhibition; (C) the case when the TKI behaves as a substrate at low concentration, where the "vacuum cleaner" model is applicable^[30]. However, when the concentration increases at a given moment saturation takes place and TKIs penetrate into the cell and bind at the NBD and thereby inhibiting the transporter. ABC: ATP-binding cassette; TKI: tyrosine kinase inhibitor; NBD: nucleotide binding domain