Figure 7.

Simplified schematic diagram of sitravatinib resensitizing multidrug-resistant cancer cells by blocking the active efflux of chemotherapeutic drugs mediated by ABCB1 and ABCG2. Normally, substrate drugs of ABCB1 (red triangles) and substrate drugs of ABCG2 (purple squares) are rapidly pumped out of a multidrug-resistant cancer cell overexpressing ABCB1 (blue) or ABCG2 (orange) and consequently leading to reduced chemosensitivity. In this model, sitravatinib (white circles) competes with the binding of substrate drugs at the substrate-binding pockets of ABCB1 and ABCG2 to increase the intracellular accumulation of therapeutic drugs and eventually restoring the chemosensitivity of multidrug-resistant cancer cells.