Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles

Abstract

The Ca²⁺ release-activated Ca²⁺ (CRAC) channels control many Ca²⁺-modulated physiological processes in mammals. Hyperactivating CRAC channels are known to cause several human diseases, including Stormorken syndrome. Here, we show the design of azopyrazole-derived photoswitchable CRAC channel inhibitors (designated <b>piCRACs</b>), which enable optical inhibition of store-operated Ca²⁺ influx and downstream signaling. Moreover, <b>piCRAC-1</b> has been applied <i>in vivo</i> to alleviate thrombocytopenia and hemorrhage in a zebrafish model of Stormorken syndrome in a light-dependent manner.