Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles

  • J Am Chem Soc. 2020 May 20;142(20):9460-9470. doi: 10.1021/jacs.0c02949.
Xingye Yang  1 ,  Guolin Ma  2 ,  Sisi Zheng  3 ,  Xiaojun Qin  1 ,  Xiang Li  1 ,  Lupei Du  1 ,  Youjun Wang  3 ,  Yubin Zhou  2 ,  Minyong Li  1  4
Affiliations
  • 1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 2. Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas 77030, United States.
  • 3. Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
  • 4. Helmholtz International Lab, State Key Laboratory of Microbial Technology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250100, China.
PMID: 32330031 DOI: 10.1021/jacs.0c02949
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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