Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 27 min ago
Peer-reviewedCC BY 4.0Angewandte Chemie (International Ed. in English)

Optical Control of the Glucocorticoid Receptor Activity With a Photoswitchable Agonist

  • Zoe Sessions1
  • Chloé Van Leene2,3,4
  • Dorien Clarisse2,3,4
  • George Keen1
  • Agnė Šveistytė5
  • Dinahlee Saturnino Guarino6
  • Robert H. Mach6
  • Karolien De Bosscher2,3,4
  • Dirk Trauner5
6 affiliations
  1. 1Department of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
  2. 2VIB‐UGent Center for Medical Biotechnology (CMB) Ghent Belgium
  3. 3Department of Biomolecular Medicine Ghent University Ghent Belgium
  4. 4Cancer Research Institute Ghent (CRIG) Ghent Belgium
  5. 5Department of Chemistry University of Pennsylvania Philadelphia Pennsylvania USA
  6. 6Department of Radiology University of Pennsylvania Philadelphia Pennsylvania USA
Read full textPDFDOICite

Abstract

Glucocorticoids (GCs) are widely prescribed anti‐inflammatory agents whose clinical utility is limited by systemic side effects arising from broad glucocorticoid receptor (GR) activation. Optical control of GR pharmacology offers a strategy to modulate receptor signaling with spatial and temporal resolution. Here, we report AzoCort1, a prednisolone‐derived photopharmaceutical that enables light‐dependent tuning of GR activity in cell culture. Upon irradiation, AzoCort1 exhibits low picomolar activity (EC50 = 11 pM) in a gene expression assay, representing a 36‐fold enhancement relative to its dark state (EC50 = 400 pM). Despite its high potency, AzoCort1 is less efficacious in triggering glucocorticoid response element (GRE)‐driven activation compared to dexamethasone, while preserving maximal GR‐dependent repression of NF‐κB and AP‐1 signaling. These findings demonstrate light‐driven control of GR activity and separation of maximal GR‐mediated gene activation from gene repression.

Related

  1. Opto-Covalent Modulators Enable Control of Endogenous Epidermal Growth Factor Receptor Activity in Native Cells
    Ziyue Wang, Xingyao Liu, Weizhi Weng +1
    ChemRxivPreprintCC BY-NC-NDFull textMaterials & polymersChemRxiv
  2. Rapid Access to Photoswitchable RNA Binders: Fluorination Enhances Protein Rescue by Exon Inclusion
    Lei Zhang, Nemanja Djokovic, Alexander Herr +8
    Chemistry (Weinheim an Der Bergstrasse, Germany)Peer-reviewedCC BY 4.0Full textMaterials & polymersPMC
  3. Optical Control of Exciton and Trap‐State Recombination in Quantum Dots Pairs Through Förster Resonance Energy Transfer
    Thomas Noblet, Marie Erard, Hippolyte Stassart +1
    Advanced Photonics ResearchPeer-reviewedPublisher termsFull text1 citedMaterials & polymersHAL
  4. Bio-Based Levoglucosenone Enables Regioisomer-Driven Inversion of Optical Activity in Polymers via Stereoselective Thia-Michael Addition of 1,2- and 1,3-Benzenedithiols
    Francesco Raboni, Shinji Kudo, Takayuki Doi +2
    ChemRxivPreprintCC BY-NC-NDFull textMaterials & polymersChemRxiv
  5. Multifunctional investigation of a chalcone derivative: nonlinear optical properties, and potent antifungal activity
    Varsha. V. Koppal, Rekha. K. Hebasur, Ninganagouda. R. Patil +7
    Scientific ReportsPeer-reviewedCC BYFull textMaterials & polymersDOAJ

Cite

BibTeXRIS
BibTeX
@article{sessions2026optical,
  title = {{Optical Control of the Glucocorticoid Receptor Activity With a Photoswitchable Agonist}},
  author = {Zoe Sessions and Chloé Van Leene and Dorien Clarisse and George Keen and Agnė Šveistytė and Dinahlee Saturnino Guarino and Robert H. Mach and Karolien De Bosscher and Dirk Trauner},
  journal = {Angewandte Chemie (International Ed. in English)},
  year = {2026},
  month = sep,
  doi = {10.1002/anie.9699968},
  url = {https://doi.org/10.1002/anie.9699968},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Optical Control of the Glucocorticoid Receptor Activity With a Photoswitchable Agonist
AU  - Zoe Sessions
AU  - Chloé Van Leene
AU  - Dorien Clarisse
AU  - George Keen
AU  - Agnė Šveistytė
AU  - Dinahlee Saturnino Guarino
AU  - Robert H. Mach
AU  - Karolien De Bosscher
AU  - Dirk Trauner
PY  - 2026
DA  - 2026/09/26
JO  - Angewandte Chemie (International Ed. in English)
DO  - 10.1002/anie.9699968
UR  - https://doi.org/10.1002/anie.9699968
AB  - Glucocorticoids (GCs) are widely prescribed anti‐inflammatory agents whose clinical utility is limited by systemic side effects arising from broad glucocorticoid receptor (GR) activation. Optical control of GR pharmacology offers a strategy to modulate receptor signaling with spatial and temporal resolution. Here, we report AzoCort1, a prednisolone‐derived photopharmaceutical that enables light‐dependent tuning of GR activity in cell culture. Upon irradiation, AzoCort1 exhibits low picomolar activity (EC50 = 11 pM) in a gene expression assay, representing a 36‐fold enhancement relative to its dark state (EC50 = 400 pM). Despite its high potency, AzoCort1 is less efficacious in triggering glucocorticoid response element (GRE)‐driven activation compared to dexamethasone, while preserving maximal GR‐dependent repression of NF‐κB and AP‐1 signaling. These findings demonstrate light‐driven control of GR activity and separation of maximal GR‐mediated gene activation from gene repression.
SN  - 1433-7851
SN  - 1521-3773
ER  -