title: 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.
  
  
  CONCLUSIONS
  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: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, via P Bucci, 87036 Rende (Cs), Italy.
authors: Marcello
authors: M
authors: Maggiolini
authors: Maria Francesca
authors: MF
authors: Santolla
authors: Silvia
authors: S
authors: Avino
authors: Francesca
authors: F
authors: Aiello
authors: Camillo
authors: C
authors: Rosano
authors: Antonio
authors: A
authors: Garofalo
authors: Fedora
authors: F
authors: Grande
mesh_terms: D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007202:Indicators and Reagents; D008024:Ligands; D011758:Pyrroles; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled