Presentation: Research and development of stimulators and activators of soluble guanylyl cyclase (sGC) in cardiorenal diseases: From basic science to therapeutic applications in HFrEF and CKD

Cardiovascular and cardiorenal diseases are amongst the most common causes of death worldwide and associated with comorbidities like hypertension, diabetes and obesity. In recent years, it was demonstrated that dysregulation of the nitric oxide (NO) – soluble guanylyl cyclase (sGC) – cyclic guanosine monophosphate (cGMP) signaling pathway plays an important role in in the development and progression of cardiovascular and cardiorenal diseases. The discovery and development of sGC stimulators and sGC activators was a milestone in the field of cGMP pharmacology allowing sustained enhancement of cGMP signaling. The presentation will summarize the NO-sGC-cGMP signaling pathway, the discovery and mechanism of action of sGC stimulators and sGC activators, as well as their development and therapeutic applications, such as chronic heart failure (HFrEF) and chronic kidney disease (CKD). A special focus will be on the effects and the mode of action of sGC activators in non-clinical models of CKD associated with diabetes and metabolic syndrome.