Description: GSK-5498A is a novel, potent and selective small molecule blocker of Calcium-Release Activated Calcium (CRAC) channel with IC50 of 1 uM; It inhibits mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species. Loss of function mutations in the two key proteins which constitute Calcium-Release Activated Calcium (CRAC) channels demonstrate the critical role of this ion channel in immune cell function. GSK-5498A was tested to demonstrate their ability to inhibit mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species. GSK-5498A completely inhibited calcium influx through CRAC channels. This led to inhibition of the release of mast cell mediators and T-cell cytokines from multiple human and rat preparations. Mast cells from guinea-pig and mouse preparations were not inhibited by GSK-5498A; however cytokine release was fully blocked from T-cells in a mouse preparation. GSK-5498A confirmed the critical role of CRAC channels in human mast cell and T-cell function, and that inhibition can be achieved in vitro. The rat displays a similar pharmacology to human, promoting this species for future in vivo research with this series of molecules. Together these observations provide a critical forward step in the identification of CRAC blockers suitable for clinical development in the treatment of inflammatory disorders.