RyR2 stabilizer-1 (Compound12a) is a potent stabilizer of RyR2 and an activator of SERCA2a, with EC50 values of 2.7 μM for RyR2 and 383 nM for SERCA2. This compound inhibits the leakage of Ca2+ through SR RyR2 while promoting the reuptake of Ca2+ into the SR by SERCA2, suggesting its potential in preventing arrhythmias.

RyR2 stabilizer-1, when administered in the range of 0-100 μM, significantly elevates [Ca 2+] ER in a dose-dependent manner, exhibiting the most pronounced effect at concentrations above 25 μM. The compound's EC50 values for SERCA2a in mouse SR, HL-1, and HEK ER are 383 nM, 9.2 μM, and 16 nM, respectively. After a 2-hour incubation with 10 μM of RyR2 stabilizer-1, an enhancement of HL-1 SERCA2a activity is observed in caffeine-induced calcium release assays. At concentrations of 0-50 μM over 24 hours in HL-1, the compound does not induce significant cell death, as evidenced by a CytoTox-Glo cytotoxicity assay. Additionally, a 5-minute exposure to 100 μM results in a marked decrease in NADH fluorescence, indicating increased SERCA2a activity in murine ventricular SR microsomes and an increase in ATPase activity.