Details

Autor(en) / Beteiligte

• Follmann, Markus
• Griebenow, Nils
• Hahn, Michael G.
• Hartung, Ingo
• Mais, Franz-Josef
• Mittendorf, Joachim
• Schäfer, Martina
• Schirok, Hartmut
• Stasch, Johannes-Peter
• Stoll, Friederike
• Straub, Alexander

Titel

The Chemistry and Biology of Soluble Guanylate Cyclase Stimulators and Activators

Ist Teil von

• Angewandte Chemie (International ed.), 2013-09, Vol.52 (36), p.9442-9462

Auflage

International ed. in English

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. A central regulator of the circulatory system is the soluble guanylate cyclase (sGC). Two compound classes have been discovered that amplify sGC function: so‐called sGC stimulators and sGC activators. Riociguat, the clinically most advanced sGC stimulator, has successfully undergone phase III trials for different forms of pulmonary hypertension and could lead to new therapies for cardiopulmonary disease.