sGC stimulator 1 is a carbonyl sulfide (COS)/H2S donor hybrid soluble guanylate cyclase (sGC) stimulator with an EC50 of 496 nM. It demonstrates significant H2S release properties and reduces fibrosis in cardiac fibroblasts treated with TGF-β1 by increasing H2S levels. sGC stimulator 1 exerts antifibrotic effects by activating sGC and elevating H2S concentrations. This compound is applicable for heart failure (HF) research[1].

sGC stimulator 1 exhibits an H2S release efficiency of up to 87% at a concentration of 25 μM. At concentrations ranging from 0-100 μM over 48 hours, this compound shows good compatibility with neonatal rat cardiac fibroblasts (CFs) without notable cytotoxicity. Additionally, when applied in the range of 5-20 μM, sGC stimulator 1 significantly elevates the intracellular cGMP levels in CFs, particularly at concentrations above 10 μM. Furthermore, within 2.5-10 μM over a 48-hour period, it effectively inhibits TGFβ1-induced α-SMA expression and FN-mediated ECM synthesis in CFs, indicating its synergistic role in suppressing CF activation.

The sGC stimulator 1, administered at doses of 3mg/kg and 5mg/kg via intraperitoneal injection once daily for three weeks, significantly improves cardiac systolic and diastolic functions in mice with heart failure induced by isoproterenol (ISO). It also reduces cardiac enlargement and ventricular remodeling while increasing plasma H2S levels in a dose-dependent manner.