Structural and molecular characterization of lopinavir and ivermectin as breast cancer resistance protein (BCRP/ABCG2) inhibitors.

ABSTRACT: A current clinical challenge in cancer is multidrug resistance (MDR) mediated by ABC transporters. Breast cancer resistance protein (BCRP) or ABCG2 transporter is one of the most important ABC transporters implicated in MDR and the use of inhibitors is a promising approach to overcome the resistance in cancer. This study aimed to characterize the molecular mechanism of ABCG2 inhibitors identified by a repurposing drug strategy using antiviral, anti-inflammatory and antiparasitic agents. Lopinavir and ivermectin can be considered as pan-inhibitors of ABC transporters, since both compounds inhibited ABCG2, P-glycoprotein and MRP1. They inhibited ABCG2 activity showing IC₅₀ values of 25.5 and 23.4 µM, respectively. These drugs were highly cytotoxic and not transported by ABCG2. Add

SUBMITTER: Dutra JP 

PROVIDER: S-EPMC10776880 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature