2. Academic Validation
  3. Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles

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

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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