The chemistry and biology of soluble guanylate cyclase stimulators and activators. 2013

Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
Bayer Pharma Aktiengesellschaft, Global Drug Discovery, Aprather Weg 18a, 42113 Wuppertal, Germany. markus.follmann@bayer.com

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.

UI MeSH Term Description Entries
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006162 Guanylate Cyclase An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. Guanyl Cyclase,Deoxyguanylate Cyclase,Guanylyl Cyclase,Inosinate Cyclase,Cyclase, Deoxyguanylate,Cyclase, Guanyl,Cyclase, Guanylate,Cyclase, Guanylyl,Cyclase, Inosinate
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071756 Soluble Guanylyl Cyclase A mammalian enzyme composed of a heterodimer of alpha and beta subunits. Each subunit consists of four domains; N-terminal HNOX domain, PAS-like domain, a coiled-coil domain, and a C-terminal catalytic domain. All four domains are homologous proteins with a similar conformation of functional domains. Soluble guanylate cyclase catalyzes the formation of cyclic GMP from GTP, and is a key enzyme of the nitric oxide signaling pathway involved in the regulation of a variety of biological and physiological processes in mammals. Nitric Oxide Receptor,Nitric Oxide Receptors,Nitric Oxide-Sensitive Guanylyl Cyclase,Receptor, Nitric Oxide,Soluble Guanylate Cyclase,Soluble Guanylyl Cyclase, alpha Subunit,Soluble Guanylyl Cyclase, beta Subunit,Cyclase, Soluble Guanylate,Cyclase, Soluble Guanylyl,Guanylate Cyclase, Soluble,Guanylyl Cyclase, Soluble,Nitric Oxide Sensitive Guanylyl Cyclase,Oxide Receptor, Nitric,Oxide Receptors, Nitric
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D055808 Drug Discovery The process of finding chemicals for potential therapeutic use. Drug Prospecting,Discovery, Drug,Prospecting, Drug
D018160 Receptors, Cytoplasmic and Nuclear Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS. Cytoplasmic Receptor,Cytoplasmic and Nuclear Receptors,Cytosolic and Nuclear Receptors,Hormone Receptors, Cytoplasmic,Hormone Receptors, Nuclear,Nuclear Hormone Receptor,Nuclear Receptor,Nuclear and Cytoplasmic Receptors,Cytoplasmic Hormone Receptors,Cytoplasmic Receptors,Cytosol and Nuclear Receptors,Intracellular Membrane Receptors,Nuclear Hormone Receptors,Nuclear Receptors,Receptors, Cytoplasmic,Receptors, Cytosol and Nuclear,Receptors, Cytosolic and Nuclear,Receptors, Intracellular Membrane,Receptors, Nuclear,Receptors, Nuclear and Cytoplasmic,Hormone Receptor, Nuclear,Membrane Receptors, Intracellular,Receptor, Cytoplasmic,Receptor, Nuclear,Receptor, Nuclear Hormone,Receptors, Cytoplasmic Hormone,Receptors, Nuclear Hormone
D020536 Enzyme Activators Compounds or factors that act on a specific enzyme to increase its activity. Activators of Enzymes,Activators, Enzyme,Enzymes Activators

Related Publications

Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
January 2021, Handbook of experimental pharmacology,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
January 2021, Handbook of experimental pharmacology,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
January 2018, Nature reviews. Urology,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
September 2021, Nature communications,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
June 2023, Current cardiology reports,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
January 2012, Critical care research and practice,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
September 2006, Nature reviews. Drug discovery,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
January 2019, Mini reviews in medicinal chemistry,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
April 2015, Current opinion in pharmacology,
Markus Follmann, and Nils Griebenow, and Michael G Hahn, and Ingo Hartung, and Franz-Josef Mais, and Joachim Mittendorf, and Martina Schäfer, and Hartmut Schirok, and Johannes-Peter Stasch, and Friederike Stoll, and Alexander Straub
March 2001, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!