Figure 7.

Model for MY-5445 resensitizing ABCG2-overexpressing cancer cells. Schematic proposing the fate of chemotherapeutic drug substrates of ABCG2 (triangles) in the absence (A) and the presence (B) of MY-5445. In the absence of MY-5445, the intracellular concentrations of chemotherapeutic drug and its cytotoxic effects are significantly reduced in these ABCG2-expressing cancer cells through direct drug efflux by ABCG2. In contrast, in the presence of MY-5445 (filled diamond), the drug efflux function of ABCG2 is blocked by MY-5445 binding to the drug-binding pocket of ABCG2. Consequently, the intracellular concentration of the chemotherapeutic drugs is restored in these multidrug-resistant cancer cells.