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Identification of Breast Cancer Inhibitors Specific for G Protein‐Coupled Estrogen Receptor (GPER)‐Expressing Cells
Author(s) -
Aiello Francesca,
Carullo Gabriele,
Giordano Francesca,
Spina Elena,
Nigro Alessandra,
Garofalo Antonio,
Tassini Sabrina,
Costantino Gabriele,
Vincetti Paolo,
Bruno Agostino,
Radi Marco
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700145
Subject(s) - gper , skbr3 , estrogen receptor , cancer research , tamoxifen , breast cancer , selective estrogen receptor modulator , cyclin d1 , receptor , estrogen , cancer cell , biology , cancer , chemistry , cell cycle , cell , endocrinology , biochemistry , human breast , genetics
Together with estrogen receptors ERα and ERβ, the G protein‐coupled estrogen receptor (GPER) mediates important pathophysiological signaling pathways induced by estrogens and is currently regarded as a promising target for ER‐negative (ER−) and triple‐negative (TN) breast cancer. Only a few selective GPER modulators have been reported to date, and their use in cancer cell lines has often led to contradictory results. Herein we report the application of virtual screening and cell‐based studies for the identification of new chemical scaffolds with a specific antiproliferative effect against GPER‐expressing breast cancer cell lines. Out of the four different scaffolds identified, 8‐chloro‐4‐(4‐chlorophenyl)pyrrolo[1,2‐ a ]quinoxaline 14 c was found to be the most promising compound able to induce: 1) antiproliferative activity in GPER‐expressing cell lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained induction of cell‐cycle negative regulators p53 and p21.