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Updated: May 13, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
CRAC inhibitors: identification and potential
Isabella Derler1, Reinhard Fritsch, Rainer Schindl
1University of Linz, Institute of Biophysics, A-4040 Linz, Austria +43 732 2468 9272 ; +43 732 2468 9280 ; isabella.derler@jku.at ; christoph.romanin@jku.at.
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.
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