Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles

Xingye Yang; Guolin Ma; Sisi Zheng; Xiaojun Qin; Xiang Li; Lupei Du; Youjun Wang; Yubin Zhou; Minyong Li

doi:10.1021/jacs.0c02949

Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles

J Am Chem Soc. 2020 May 20;142(20):9460-9470. doi: 10.1021/jacs.0c02949. Epub 2020 May 6.

Authors

Xingye Yang¹, Guolin Ma², Sisi Zheng³, Xiaojun Qin¹, Xiang Li¹, Lupei Du¹, Youjun Wang³, Yubin Zhou², 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.

Publication types

Research Support, Non-U.S. Gov't