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 journalArticle

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

  • Chemistry(all)

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    Morstein, J., Trads, J. B., Hinnah, K., Willems, S., Barber, D. M., Trauner, M., Merk, D., & Trauner, D. (2020). Optical control of the nuclear bile acid receptor FXR with a photohormone. Chemical Science, 11(2), 429-434. https://doi.org/10.1039/c9sc02911g