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

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.

• Authors: Marcello Maggiolini, Maria Francesca Santolla, Silvia Avino, Francesca Aiello, Camillo Rosano, Antonio Garofalo, Fedora Grande
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 7 Issue 4 Pg. 437-48 ( 2015) ISSN: 1756-8927 [Electronic] England
• PMID: 25875871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indicators and Reagents
• Ligands
• Pyrroles
• Receptors, Estrogen
• Receptors, G-Protein-Coupled

Topics

• Binding, Competitive
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Female
• Fibroblasts (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Indicators and Reagents
• Ligands
• Models, Molecular
• Molecular Conformation
• Pyrroles (chemical synthesis, pharmacology)
• Receptors, Estrogen (antagonists & inhibitors)
• Receptors, G-Protein-Coupled (antagonists & inhibitors)
• Signal Transduction (drug effects)