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Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles
Xingye Yang1, Guolin Ma2, Sisi Zheng3
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
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 piCRACs), which enable optical inhibition of store-operated Ca2+ influx and downstream signaling. Moreover, piCRAC-1 has been applied in vivo to alleviate thrombocytopenia and hemorrhage in a zebrafish model of Stormorken syndrome in a light-dependent manner.
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