SN-6 is a selective Na+/Ca2+ exchanger (NCX) inhibitor, inhibits Ca2+ uptake by NCX1, NCX2, and NCX3 with IC50 of 2.9, 16, and 8.6 uM, respectively. SN-6 (0.3-30 uM) inhibits preferentially intracellular Na(+)-dependent (45)Ca(2+) uptake (i.e., the reverse mode) compared with extracellular Na(+)-dependent (45)Ca(2+) efflux (i.e., the forward mode) in NCX1-transfected fibroblasts. SN-6 is 3- to 5-fold more inhibitory to (45)Ca(2+) uptake in NCX1 (IC(50) = 2.9 uM) than to that in NCX2 or NCX3 but not to that in NCKX2. SN-6 at lower doses (IC(50) = 0.63 uM) potently protects against hypoxia/reoxygenation-induced cell damage in renal tubular cells overexpressing NCX1, suggesting that this drug predominantly works under hypoxic/ischemic conditions.
