Optical control of the nuclear bile acid receptor FXR with a photohormone
Creators
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1.
New York University
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2.
California Institute of Technology
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.
Copyright and License
This article is Open Access. All publication charges for this article have been paid for by the Royal Society of Chemistry
Files
c9sc02911g.pdf
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Additional details
Identifiers
- ISSN
- 2041-6539
Related works
- Is supplemented by
- Supplemental Material: https://www.rsc.org/suppdata/c9/sc/c9sc02911g/c9sc02911g1.pdf (URL)
Funding
- New York University
- Margaret and Herman Sokol Fellowship
- European Commission
- Marie Sklodowska Curie-Fellowship PIEF-GA-2013-627
- Danish National Research Foundation
- DNRF81
- Aarhus University
Dates
- Accepted
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2019-11-04Accepted
- Available
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2019-11-19First published