GSK7975A

GSK7975A is a potent and selective small molecule inhibitor of Calcium Release-Activated Calcium (CRAC) channels, specifically targeting the ORAI1 and ORAI3 subunits. It acts by blocking store-operated calcium entry (SOCE), a process where the depletion of endoplasmic reticulum calcium stores triggers the influx of extracellular calcium. Developed by GSK, the compound is extensively used as a pharmacological tool in research to investigate the role of calcium signaling in various pathologies, including inflammation, acute pancreatitis, and cancer. Recent studies presented at AACR 2025 have demonstrated its ability to sensitize melanoma and colon adenocarcinoma cells to ferroptosis—an iron-dependent form of regulated cell death—by modulating cellular calcium homeostasis and lipid peroxidation levels.