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

Johannes Morstein, Julie B. Trads, Konstantin Hinnah, Sabine Willems, David M. Barber, Michael Trauner, Daniel Merk, Dirk Trauner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)429-434
Number of pages6
JournalChemical Science
Volume11
Issue number2
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • General Chemistry

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