The results of the accumulation and efflux experiments were congruent with the reversal effects of VS-4718 shown in anti-cancer efficacy testing when co-administered with substrate-drugs, suggesting that VS-4718 may increase the accumulation of substrate-drugs in ABCB1- and ABCG2-overexpressing cancer cells by inhibiting the ABCB1- and ABCG2-mediated efflux activity, which led to the decline of IC50 of substrate-drugs and finally attenuated the ABC transporter-mediated MDR. Here, ABCG2 is linked to cancer.