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.
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: Chelsea DeLeon; Helen H Wang; Joseph Gunn; McKenna Wilhelm; Aidan Cole; Stacy Arnett; David Q-H Wang; Christopher K Arnatt Journal: J Lipid Res Date: 2020-03-03 Impact factor: 5.922
Authors: Nathalie Sumien; J Thomas Cunningham; Delaney L Davis; Rachel Engelland; Oluwadarasimi Fadeyibi; George E Farmer; Steve Mabry; Paapa Mensah-Kane; Oanh T P Trinh; Philip H Vann; E Nicole Wilson; Rebecca L Cunningham Journal: Endocrinology Date: 2021-11-01 Impact factor: 5.051
Authors: Aldo Moreno-Ulloa; David Mendez-Luna; Ernesto Beltran-Partida; Carmen Castillo; Gustavo Guevara; Israel Ramirez-Sanchez; José Correa-Basurto; Guillermo Ceballos; Francisco Villarreal Journal: Pharmacol Res Date: 2015-08-21 Impact factor: 7.658
Authors: M F Santolla; S Avino; M Pellegrino; E M De Francesco; P De Marco; R Lappano; A Vivacqua; F Cirillo; D C Rigiracciolo; A Scarpelli; S Abonante; M Maggiolini Journal: Cell Death Dis Date: 2015-07-30 Impact factor: 8.469