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

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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.

Graphical abstract: Optical control of the nuclear bile acid receptor FXR with a photohormone

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Publication details

The article was received on 14 Jun 2019, accepted on 04 Nov 2019 and first published on 19 Nov 2019


Article type: Edge Article
DOI: 10.1039/C9SC02911G
Chem. Sci., 2020, Advance Article
  • Open access: Creative Commons BY license
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    Optical control of the nuclear bile acid receptor FXR with a photohormone

    J. Morstein, J. B. Trads, K. Hinnah, S. Willems, D. M. Barber, M. Trauner, D. Merk and D. Trauner, Chem. Sci., 2020, Advance Article , DOI: 10.1039/C9SC02911G

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