Exploring the Potential of TY-55002: A Short-Acting sGC Activator for Acute Decompensated Heart Failure Management

The study explores the effects of a new short-acting soluble guanylate cyclase (sGC) activator, TY-55002, in acute decompensated heart failure (ADHF) patients. The research aimed to determine if TY-55002 could induce vasodilation without causing hypotension, unlike cinaciguat, which was previously discontinued due to this side effect. Both TY-55002 and cinaciguat were found to activate normal and heme-oxidized sGC, leading to the relaxation of contracted rat aorta. However, TY-55002 demonstrated a less pronounced effect on the dose-response between normal and oxidized sGC, suggesting it may be less affected by oxidative stress related to conditions like cardiovascular disease or diabetes.

In normal dogs, the impact of intravenous TY-55002 and cinaciguat on blood pressure was assessed alongside their plasma levels. Pharmacokinetic-pharmacodynamic (PK-PD) analyses revealed that TY-55002 had a significantly higher plasma-to-effect-site transfer rate constant (Ke0) than cinaciguat, although there was only a slight variation in their blood half-life (T1/2). This indicates that the rapid initial drop in blood pressure and swift recovery following TY-55002 administration could be attributed to its pharmacodynamic properties.

In dogs with heart failure, both TY-55002 and cinaciguat showed similar improvements in the condition, with TY-55002's short-term effects being consistent. The study concludes that TY-55002, as a novel sGC activator, provides an easy-to-manage dosage option that minimizes the risk of excessive hypotension, making it a promising candidate for the treatment of ADHF.