CMP25, a synthetic new agent, targets multidrug resistance-associated protein 7 (MRP7/ABCC10)

Multidrug resistance-associated protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to mediate the cross-membrane translocation of a wide range of chemotherapeutic agents including taxanes, epothilones, Vinca alkaloids, Anthracyclines and Epipodophyllotoxins. In our previous study, a 1,2,3-triazole-pyrimidine hybrid CMP25 was synthesized and found able to efficiently reverse multidrug resistance (MDR) mediated by P-glycoprotein. In this study, we evaluated the efficacy of compound CMP25 in reversing MDR mediated by MRP7 in vitro. The results showed that CMP25 significantly sensitized MRP7overexpressing cells to anticancer drugs that are MRP7 substrates. Mechanistic study showed that CMP25 reversed MRP7-mediated MDR by increasing the intracellular accumulation of anticancer drugs and decreasing drug efflux, without altering protein expression level or subcellular localization. Currently, very few studies on synthetic MRP7 modulators have been published. Our findings provide a valuable prototype for designing drugs to combine with conventional anticancer drugs to overcome MDR-mediated by MRP7.

Automated summary

The synthesized compound CMP25 was found to reverse MDR mediated by MRP7 by increasing intracellular accumulation of anticancer drugs and decreasing drug efflux. This suggests that CMP25 could be a useful prototype for designing drugs to combine with conventional anticancer drugs.