Abstract
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.
Financial & competing interests disclosure
This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, project n. 12849/2012), AIRC project Calabria 2011 (www.airc.it/) and Fondazione Cassa di Risparmio di Calabria e Lucania CR. The authors thank the ‘Compagnia di San Paolo di Torino’ for the generous support to this research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.