Photopharmacological modulation of native CRAC channels using azoboronate photoswitches.
Ronald UdasinAnwesha SilElia ZomotHadas Achildiev CohenJozafina HajNurit EngelmayerShaya LevAlexander M BinshtokYuval ShakedMichael A KienzlerRaz PaltyPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
SignificanceCalcium release-activated calcium (CRAC) channels play key roles in the regulation of cellular signaling, transcription, and migration. Here, we describe the design, chemical synthesis, and characterization of photoswitchable channel inhibitors that can be switched on and off depending on the wavelength of light used. We use the compounds to induce light-dependent modulation of channel activity and downstream gene expression in human immune cells. We further expand the usage of the compounds to control seeding of cancer cells in target tissue and regulation of response to noxious stimuli in vivo in mice.