JK-2 is a phosphorothioate-based hydrogen sulfide (H2S) donor that shows greatly accelerated H2S release upon protonation-induced intramolecular cyclization at acidic pH ([H2S]/time/pH = 94 µM/4.5 min/pH 5.0, 84 µM/4.5 min/pH 6.0, 36 µM/90 min/pH 7.4, 21 µM/90 min/pH 8.0 with JK-2; [JK-2] = 100 µM at time 0) and is superior to GYY4137 in H2S generation both in buffer (﹤5 µM H2S/90 min/pH 5.0-8.0 with GYY4137) and in cells without cytotoxicity up to 400 µM in H9c2 and HeLa cultures. JK-2 protects H9c2 rat myoblasts from anoxia/reoxygenation (A/R; 1 hr 2% O2, then 6 hr reoxygenation with 400 µM H2O2) treatment (100% vs. 60% viability with or without 25 µM JK-2) and is efficacious in reducing infarct size per area-at-risk (INF/AAR) upon myocardial ischemia-reperfusion (MI/R) injury induction in mice invivo (55% and 56% INF/AAR redcution with 50 µg/kg and 100 µg/kg, respectively, via intracardiac injection).