Fig. 7. A schematic diagram illustrating how SIS3 reverses drug resistance mediated by ABCB1 and ABCG2.

In the absence of SIS3 (left panel), ABCB1 substrate drugs (green circles) and ABCG2 substrate drugs (gray circles) are actively pumped out by ABCB1 (orange) and ABCG2 (blue), respectively, resulting in reduced intracellular drug accumulation and drug resistance. In contrast, in the presence of SIS3 (right panel), ABCB1 substrate drugs and ABCG2 substrate drugs are no longer able to access the drug binding pockets of ABCB1 and ABCG2 since SIS3 (white squares) has already occupied the sites, consequently restoring intracellular drug concentration and chemosensitivity.