Soluble guanylate cyclase stimulators and activators, such as riociguat, amplify sGC function in an NO-independent manner to overcome the therapeutic shortcomings of traditional NO-donor drugs.
Soluble guanylate cyclase stimulators and activators represent a novel NO-independent therapeutic approach for cardiovascular diseases, particularly pulmonary hypertension.
The vasodilatory properties of nitric oxide (NO) have been utilized in pharmacotherapy for more than 130 years. Still today, NO-donor drugs are important in the management of cardiovascular diseases. However, inhaled NO or drugs releasing NO and organic nitrates are associated with noteworthy therapeutic shortcomings, including resistance to NO in some disease states, the development of tolerance during long-term treatment, and nonspecific effects, such as post-translational modification of proteins. The beneficial actions of NO are mediated by stimulation of soluble guanylate cyclase (sGC), a heme-containing enzyme which produces the intracellular signaling molecule cyclic guanosine monophosphate (cGMP). Recently, two classes of compounds have been discovered that amplify the function of sGC in a NO-independent manner, the so-called sGC stimulators and sGC activators. The most advanced drug, the sGC stimulator riociguat, has successfully undergone Phase III clinical trials for different forms of pulmonary hypertension.
Follmann et al. (Tue,) conducted a review in Cardiovascular diseases and pulmonary hypertension. Soluble Guanylate Cyclase (sGC) Stimulators and Activators was evaluated. Soluble guanylate cyclase stimulators and activators, such as riociguat, amplify sGC function in an NO-independent manner to overcome the therapeutic shortcomings of traditional NO-donor drugs.