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The Chemistry and Biology of Soluble Guanylate Cyclase Stimulators and Activators
Author(s) -
Follmann Markus,
Griebenow Nils,
Hahn Michael G.,
Hartung Ingo,
Mais FranzJosef,
Mittendorf Joachim,
Schäfer Martina,
Schirok Hartmut,
Stasch JohannesPeter,
Stoll Friederike,
Straub Alexander
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201302588
Subject(s) - guanylate cyclase , riociguat , cyclic guanosine monophosphate , nitric oxide , intracellular , pharmacology , gucy1a3 , guanosine , chemistry , vasodilation , soluble guanylyl cyclase , gucy1b3 , medicine , biochemistry , guanylate cyclase 2c
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.