Estrogens control a wide number of aspects of human physiology and play a key role in
multiple diseases, including cancer. Estrogens act by binding to and activating the cognate receptor
(ER), however numerous studies have revealed that the G protein-coupled receptor named
GPR30/GPER mediates also estrogen signals. As ER and GPER share the ability to bind to same compounds, the use of
GPER-selective ligands has allowed a better understanding of the biological responses mediated by GPER. In the present
study, we designed and synthesized two novel carbazole derivatives and then investigated their ability to interact with and
activate the GPER-mediated transduction pathway in breast cancer cells. Both compounds did not activate the classical
ER in MCF7 cells, whereas one of the two compounds synthesized triggered through GPER the rapid ERK activation in
ER-negative SkBr3 cells, demonstrating a good affinity for GPER in docking studies. The characterization of this novel
selective GPER agonist could represent a potential useful tool to provide further insights into the physiopathological role
exerted by GPER.
Keywords: Breast cancer, Carbazole derivatives, Docking simulations, Estrogen/estrogen receptors, GPR30/GPER, Heterocycles.
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