Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles

作者：Xingye Yang, Guolin Ma, Sisi Zheng, Xiaojun Qin, Xiang Li, Lüpei Du, Youjun Wang, Yubin Zhou, Minyong Li · 发表于：Journal of the American Chemical Society · 年份：2020 · DOI：10.1021/jacs.0c02949 · 被引用次数：50 · 研究领域：Photochromic and Fluorescence Chemistry、Neurobiology and Insect Physiology Research、Photoreceptor and optogenetics research

The Ca 2+ release-activated Ca 2+ (CRAC) channels control many Ca 2+ -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 Ca 2+ 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.