Optical control of the nuclear bile acid receptor FXR with a photohormone. Issue 2 (22nd November 2019)

• Record Type: Journal Article
• Authors: Morstein, Johannes; Trads, Julie B.; Hinnah, Konstantin; Willems, Sabine; Barber, David M.; Trauner, Michael; Merk, Daniel; Trauner, Dirk
• Is Part Of: Chemical science. Volume 11:Issue 2(2020)
• Page Start: 429
• Page End: 434
• Publication Date: 2019-11-22
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9sc02911g
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Herein, we report a photoswitchable modulator for a nuclear hormone receptor that exerts its hormonal effects in a light-dependent fashion. Abstract : Herein, we report a photoswitchable modulator for a nuclear hormone receptor that exerts its hormonal effects in a light-dependent fashion. The azobenzene AzoGW enables optical control of the farnesoid X receptor (FXR), a key regulator of hepatic bile acid, lipid and glucose metabolism. AzoGW 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 ( CYP7A1, Ostα, Ostβ ) in liver cells.