CRAC inhibitors: identification and potential

Abstract

Background: Ca²⁺ release-activated Ca²⁺ (CRAC) channels, a subfamily of store-operated channels, play an essential role in various diseases such as immune disorders and allergic responses. Objective: The successful treatment of these diseases requires the identification of specific inhibitors. So far, a variety of chemical compounds blocking CRAC have been identified; however, they have all turned out to be less specific. Recently two proteins, STIM1 and ORAI1, have been identified as the essential components that fully reconstitute CRAC currents with a similar biophysical fingerprint. Method: These two proteins and their activation process represent direct targets for the application of specific CRAC inhibitors. Results/conclusion: For drug development, fluorescence microscopy adaptable for high-throughput screening will provide a powerful assay to mechanistically identify potential CRAC inhibitors that act on various stages within the STIM1/ORAI1 activation pathway visualized by fluorescent-tagged proteins.

Keywords::

• Ca²⁺ release-activated Ca²⁺
• fluorescence resonance energy transfer
• ORAI
• store-operated channel
• stromal interaction molecule

Notes