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Updated: Oct 28, 2026

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
Published on: May 24, 2024
Store-Operated Calcium Entry Inhibitors: Structural Diversity, Mechanisms of Action, and Optimization Strategies
Anastasiia A Zakharova1, Dmitriy A Grekhnev1, Elena V Kaznacheyeva1,2
1Institute of Cytology of Russian Academy of Science, Tikhoretsky Ave. 4, 194064 St. Petersburg, Russia.
Abstract:
Store-operated calcium entry (SOCE) is a ubiquitous calcium influx pathway critically involved in numerous physiological processes. Dysregulated SOCE contributes to the pathogenesis of cardiovascular disorders, cancer, and neurodegenerative diseases, making SOCE modulators promising therapeutic candidates. This review provides an overview of the major chemical classes of classical SOCE inhibitors that target Orai and STIM proteins. We focus on structure-activity relationships (SARs), mechanisms of action, strategies for enhancing inhibitory potency and selectivity, and discuss the limitations and side-effect profiles of these compounds. This comprehensive analysis identifies SOC channels as promising therapeutic targets and outlines future directions for rational drug design and the development of clinically viable SOCE modulators.
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