Targeting breast cancer resistance protein (BCRP/ABCG2): Functional inhibitors and expression modulators

Eur J Med Chem. 2022 Apr 6;237:114346. doi: 10.1016/j.ejmech.2022.114346. Online ahead of print.ABSTRACTThe primary source of failure of cancer therapies is multidrug resistance (MDR), which can be caused by different mechanisms, including the overexpression of ABC transporters in cancer cells. Among the 48 human ABC proteins, the breast cancer resistance protein (BCRP/ABCG2) has been described as a pivotal player in cancer resistance. The use of functional inhibitors and expression modulators is a promising strategy to overcome the MDR caused by ABCG2. Despite the lack of clinical trials using ABCG2 inhibitors, many compounds have already been discovered. This review presents an overview about various ABCG2 inhibitors that have been identified, discussing some chemical aspects and the main experimental methods used to identify and characterize the mechanisms of new inhibitors. In addition, some biological requirements to pursue preclinical tests are described. Finally, we discuss the potential use of ABCG2 inhibitors in cancer stem cells (CSC) for improving the objective response rate and the mechanism of ABCG2 modulators at transcriptional and protein expression levels.PMID:35483322 | DOI:10.1016/j.ejmech.2022.114346

Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Ingrid Fatima Zattoni Let ícia Carani Delabio Julia de Paula Dutra Diogo Henrique Kita Gustavo Scheiffer Marina Hembecker Giovana da Silva Pereira Vivian Rotuno Moure Glaucio Valdameri Source Type: research