Store-Operated Crac Channel Inhibitors: Opportunities and Challenges

Abstract

Aberrant Ca²⁺ release-activated Ca²⁺ (CRAC) channel activity has been implicated in a number of human disorders, including immunodeficiency, autoimmunity, occlusive vascular diseases and cancer, thus placing CRAC channels among the important targets for the treatment of these disorders. We briefly summarize herein the molecular basis and activation mechanism of CRAC channel and focus on discussing several pharmacological inhibitors of CRAC channels with respect to their biological activity, mechanisms of action and selectivity over other types of Ca²⁺ channel in different types of cells.

Keywords::

• Ca2⁺ release-activated Ca²⁺ channel
• CRAC channel inhibitor
• ORAI1
• STIM1
• store-operated Ca²⁺ entry

Financial & competing interests disclosure

This work and the authors of this manuscript have been supported by the Major Project of Science and Technology of Shandong Province (2015ZDJS04001), the Fundamental Research Funds of Shandong University (2014JC008) and the NIH (R01GM112003). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work and the authors of this manuscript have been supported by the Major Project of Science and Technology of Shandong Province (2015ZDJS04001), the Fundamental Research Funds of Shandong University (2014JC008) and the NIH (R01GM112003). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.