RO2959 inhibits Orai1 and Orai3 with IC ₅₀ values of 25 nM and 530 nM, respectively. RO2959 blocks store operated calcium entry (SOCE) in activated CD4+T lymphocytes with an IC ₅₀ value of 265 nM.
RO2959 is a potent SOCE inhibitor that blocks an IP3-dependent current in CRAC-expressing RBL-2H3 cells and CHO cells stably expressing human Orai1 and Stim1, as well as SOCE in human primary CD4 ⁺ T cells triggered by either T cell receptor (TCR) stimulation or thapsigargin treatment. RO2959 completely inhibits cytokine production as well as T cell proliferation mediated by TCR stimulation or MLR (mixed lymphocyte reaction).