Identification of two benzopyrroloxazines acting as selective GPER antagonists in breast cancer cells and cancer-associated fibroblasts

Marcello Maggiolini, Maria Francesca Santolla, Silvia Avino, Francesca Aiello, Camillo Rosano, Antonio Garofalo, Fedora Grande

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)437-448
Number of pages12
JournalFuture Medicinal Chemistry
Volume7
Issue number4
DOIs
Publication statusPublished - Mar 1 2015

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Molecular Medicine

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