Morstein Johannes, Trads Julie B, Hinnah Konstantin, Willems Sabine, Barber David M, Trauner Michael, Merk Daniel, Trauner Dirk
Department of Chemistry , New York University , New York , New York 10003 , USA . Email:
Department of Chemistry , Center for Integrated Protein Science , Ludwig Maximilians University Munich , 81377 Munich , Germany.
Chem Sci. 2019 Nov 19;11(2):429-434. doi: 10.1039/c9sc02911g. eCollection 2020 Jan 14.
Herein, we report a photoswitchable modulator for a nuclear hormone receptor that exerts its hormonal effects in a light-dependent fashion. The azobenzene enables optical control of the farnesoid X receptor (FXR), a key regulator of hepatic bile acid, lipid and glucose metabolism. was derived from the synthetic agonist GW4064 through an azologization strategy and is a metabolically stable, highly selective photoswitchable FXR agonist in its dark-adapted form. Upon irradiation, the thermally bistable 'photohormone' becomes significantly less active. Optical control of FXR was demonstrated in a luminescence reporter gene assay and through light-dependent reversible transcription modulation of FXR target genes (, , ) in liver cells.
在此，我们报道了一种用于核激素受体的光开关调节剂，其以光依赖方式发挥激素作用。偶氮苯能够对法尼醇X受体（FXR）进行光学控制，FXR是肝脏胆汁酸、脂质和葡萄糖代谢的关键调节因子。它是通过偶氮化策略从合成激动剂GW4064衍生而来，在暗适应形式下是一种代谢稳定、高度选择性的光开关FXR激动剂。照射后，热双稳态的“光激素”活性显著降低。在发光报告基因测定中以及通过肝细胞中FXR靶基因（，，）的光依赖可逆转录调节证明了对FXR的光学控制。
