Quinoline Carboxamide-Type ABCG2 Modulators: Indole and Quinoline Moieties as Anilide Replacements

摘要

The ATP-driven drug efflux transporters ABCB1 (p-glycoprotein, p-gp), ABCC1 (MRP1), and ABCG2 (breast cancer resistance protein, BCRP) play an important role in multidrug resistance (MDR) of cancer. In addition, the chemotherapy of malignant central nervous system (CNS) tumors is compromised due to the expression of ABC proteins at the blood-brain barrier, restricting the access of many potent cytostatics to the brain, in the case that these compounds are substrates of the respective pumps. The coadministration of such cytostatics with inhibitors of efflux transporters represents an attractive strategy to overcome the blood-brain barrier and to improve chemotherapy of malignancies in the CNS, as demonstrated in a proof-of-concept study for ABCB1. It is expected that this concept is also applicable to ABCG2, provided that appropriate inhibitors are available.