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Optical control of the nuclear bile acid receptor FXR with a photohormone.

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, Ost?, Ost?) in liver cells.

SUBMITTER: Morstein J

PROVIDER: S-EPMC7067245 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Optical control of the nuclear bile acid receptor FXR with a photohormone.

Morstein Johannes J Trads Julie B JB Hinnah Konstantin K Willems Sabine S Barber David M DM Trauner Michael M Merk Daniel D Trauner Dirk D

Chemical science 20191119 2

Herein, we report a photoswitchable modulator for a nuclear hormone receptor that exerts its hormonal effects in a light-dependent fashion. The azobenzene <b>AzoGW</b> enables optical control of the farnesoid X receptor (FXR), a key regulator of hepatic bile acid, lipid and glucose metabolism. <b>AzoGW</b> 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 irrad ...[more]

PMID: 32190263

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