TY - JOUR
T1 - Identification of two benzopyrroloxazines acting as selective GPER antagonists in breast cancer cells and cancer-associated fibroblasts
AU - Maggiolini, Marcello
AU - Santolla, Maria Francesca
AU - Avino, Silvia
AU - Aiello, Francesca
AU - Rosano, Camillo
AU - Garofalo, Antonio
AU - Grande, Fedora
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Background: G-protein coupled estrogen receptor (GPER) is involved in numerous intracellular physiological and pathological events including cancer cell migration and proliferation. Its characterization is yet incomplete due to the limited number of specific ligands. Results: Two novel selective GPER antagonists, based on a benzo[b]pyrrolo[1,2-d][1,4]oxazin-4-one structure, have been designed and synthesized. Their binding to the receptor was confirmed by a competition assay, while the antagonist effects were ascertained by their capability to prevent the ligand-stimulated action of GPER. The transcription mediated by the classical estrogen receptor was not influenced, demonstrating selectivity for GPER. Conclusion: These novel compounds may be considered useful leads toward the dissection of the GPER signaling and the development of new pharmacological treatments in breast cancer.
AB - Background: G-protein coupled estrogen receptor (GPER) is involved in numerous intracellular physiological and pathological events including cancer cell migration and proliferation. Its characterization is yet incomplete due to the limited number of specific ligands. Results: Two novel selective GPER antagonists, based on a benzo[b]pyrrolo[1,2-d][1,4]oxazin-4-one structure, have been designed and synthesized. Their binding to the receptor was confirmed by a competition assay, while the antagonist effects were ascertained by their capability to prevent the ligand-stimulated action of GPER. The transcription mediated by the classical estrogen receptor was not influenced, demonstrating selectivity for GPER. Conclusion: These novel compounds may be considered useful leads toward the dissection of the GPER signaling and the development of new pharmacological treatments in breast cancer.
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U2 - 10.4155/fmc.15.3
DO - 10.4155/fmc.15.3
M3 - Article
C2 - 25875871
AN - SCOPUS:84928168009
VL - 7
SP - 437
EP - 448
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
SN - 1756-8919
IS - 4
ER -