New photo-pharmacology prototype publication
New photo-pharmacology prototype publication
Drug Screening Newsletter 2024 | Issue #1
Drug Screening Newsletter 2024 | Issue #1
In the latest publication in ACS Chemical Neuroscience, Dr. Guillaume Lebon and his team from Institut de Génomique Fonctionnelle, Montpellier use an external illumination prototype with FDSS/µCELL for opto-pharmacology. The study investigates the light sensitivity of the FDA-approved antagonist istradefylline for neurodegenerative diseases and cancer treatment. It reveals its rapid response to UV light, enabling real-time control of A2AR signaling in cells and zebrafish.
In recent years, there has been growing interest in the potential therapeutic use of inhibitors of adenosine A2A receptors (A2AR) for the treatment of neurodegenerative diseases and cancer. Nevertheless, the widespread expression of A2AR throughout thbody emphasizes the importance of temporally and spatially selective ligands. Photopharmacology is an emerging strategy that utilizes photosensitive ligands to attain high spatiotemporal precision and regulate the function of biomolecules using light. In this study, we combined photochemistry and cellular and in vivo photopharmacology to investigate the light sensitivity of the FDA-approved antagonist istradefylline and its potential use as an A2AR photopharmacological tool. Our findings reveal that istradefylline exhibits rapid trans-to-cis isomerization under near-UV light, and prolonged exposure results in the formation of photocycloaddition products. We demonstrate that exposure to UV light triggers a time-dependent decrease in the antagonistic activity of istradefylline in A2AR-expressing cells and enables real-time optical control of A2AR signaling in living cells and zebrafish. Together, these data demonstrate that istradefylline is a photoinactivatable A2AR antagonist and that this property can be utilized to perform photopharmacological experiments in living cells and animals.
External illumination
2 LED Colors by well
395 nm & 480 nm
Real time addition of compound with FDSSµcell (96 head) with external illumination
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