CRAC inhibitors: identification and potential

BACKGROUND: Ca(2+) release-activated Ca(2+) (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.