Cancer Therapy Potential Unveiled: FDA‐Approved Drugs Targeting Glutaminase for Breast Cancer Treatment

Abstract

AbstractThe survival and proliferation of proliferating cancer cells is largely dependent on glutamine. Glutamine serves as a nitrogen source for the synthesis of amino acids and nucleotides, and as a carbon source for the synthesis of lipids. Virtual screening of FDA‐approved drugs is a promising approach to identify new glutaminase inhibitors. In this study, molecular docking were used to screen a library of FDA‐approved drugs against glutaminase. Their potential as inhibitors for the treatment of breast cancer was evaluated. Molecular dynamics simulations were performed on promising candidates. An in vitro study using two breast cancer cell lines, MDA‐MB‐231 and MCF‐7, was performed to evaluate the effect of the selected drugs on cell viability and expression of apoptosis‐related genes. Our results identified several FDA‐approved drugs with potential inhibitory activity against glutaminase, including bromocriptine, doxycycline, dutasteride, ezetimibe, fexofenadine, montelukast, pimozide, and tetracycline. In vitro assays revealed a dose‐dependent inhibitory effect of rifampin and bromocriptine, two drugs with the highest binding affinity to glutaminase, on cell viability and apoptosis‐related genes in breast cancer cell lines. Targeting glutaminase with FDA‐approved drugs may be a promising strategy for the development of new cancer therapies, especially for breast cancer.