Maggiolini Marcello, Santolla Maria Francesca, Avino Silvia, Aiello Francesca, Rosano Camillo, Garofalo Antonio, Grande Fedora
Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, via P Bucci, 87036 Rende (Cs), Italy.
Future Med Chem. 2015;7(4):437-48. doi: 10.4155/fmc.15.3.
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.
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.
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.
G蛋白偶联雌激素受体（GPER）参与众多细胞内生理和病理事件，包括癌细胞迁移和增殖。由于特异性配体数量有限，其特性尚未完全明确。
设计并合成了两种基于苯并[b]吡咯并[1,2-d][1,4]恶嗪-4-酮结构的新型选择性GPER拮抗剂。通过竞争试验证实了它们与受体的结合，同时通过其阻止GPER配体刺激作用的能力确定了拮抗剂作用。经典雌激素受体介导的转录未受影响，表明对GPER具有选择性。
这些新型化合物可能被认为是用于剖析GPER信号传导和开发乳腺癌新药物治疗的有用先导物。
