Interfacial residues promote an optimal alignment of the catalytic center in soluble guanylate cyclase

Nitric Oxide ◽  
2014 ◽  
Vol 42 ◽  
pp. 112
Author(s):  
Elsa Garcin ◽  
Franziska Seeger ◽  
Royston Quintyn ◽  
Akiko Tanimoto ◽  
Gareth Williams ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Optimal Alignment ◽  
Catalytic Center

scholarly journals Interfacial Residues Promote an Optimal Alignment of the Catalytic Center in Human Soluble Guanylate Cyclase: Heterodimerization Is Required but Not Sufficient for Activity

Biochemistry ◽  
2014 ◽  
Vol 53 (13) ◽  
pp. 2153-2165 ◽  
Author(s):  
Franziska Seeger ◽  
Royston Quintyn ◽  
Akiko Tanimoto ◽  
Gareth J. Williams ◽  
John A. Tainer ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Optimal Alignment ◽  
Catalytic Center ◽  
Human Soluble Guanylate Cyclase

Interfacial residues promote an optimal alignment of the catalytic center in soluble guanylate cyclase

Nitric Oxide ◽  
2014 ◽  
Vol 42 ◽  
pp. 152-153
Author(s):  
Elsa Garcin ◽  
Franziska Seeger ◽  
Royston Quintyn ◽  
Akiko Tanimoto ◽  
Gareth Williams ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Optimal Alignment ◽  
Catalytic Center

Soluble Guanylate Cyclase Stimulators and Activators: Where are We and Where to Go?

2019 ◽  
Vol 19 (18) ◽  
pp. 1544-1557 ◽  
Author(s):  
Sijia Xiao ◽  
Qianbin Li ◽  
Liqing Hu ◽  
Zutao Yu ◽  
Jie Yang ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Muscle Relaxation ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Smooth Muscle Relaxation ◽  
Secondary Messenger ◽  
Physiological Processes ◽  
Cgmp Pathway ◽  
Preclinical And Clinical Studies

Soluble Guanylate Cyclase (sGC) is the intracellular receptor of Nitric Oxide (NO). The activation of sGC results in the conversion of Guanosine Triphosphate (GTP) to the secondary messenger cyclic Guanosine Monophosphate (cGMP). cGMP modulates a series of downstream cascades through activating a variety of effectors, such as Phosphodiesterase (PDE), Protein Kinase G (PKG) and Cyclic Nucleotide-Gated Ion Channels (CNG). NO-sGC-cGMP pathway plays significant roles in various physiological processes, including platelet aggregation, smooth muscle relaxation and neurotransmitter delivery. With the approval of an sGC stimulator Riociguat for the treatment of Pulmonary Arterial Hypertension (PAH), the enthusiasm in the discovery of sGC modulators continues for broad clinical applications. Notably, through activating the NO-sGC-cGMP pathway, sGC stimulator and activator potentiate for the treatment of various diseases, such as PAH, Heart Failure (HF), Diabetic Nephropathy (DN), Systemic Sclerosis (SS), fibrosis as well as other diseases including Sickle Cell Disease (SCD) and Central Nervous System (CNS) disease. Here, we review the preclinical and clinical studies of sGC stimulator and activator in recent years and prospect for the development of sGC modulators in the near future.

scholarly journals Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042)

2021 ◽  
Author(s):  
Michael G. Hahn ◽  
Thomas Lampe ◽  
Sherif El Sheikh ◽  
Nils Griebenow ◽  
Elisabeth Woltering ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Guanylate Cyclase Activator ◽  
Cyclase Activator

scholarly journals Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3418
Author(s):  
Grzegorz Grześk ◽  
Alicja Nowaczyk
Keyword(s):  
Guanylate Cyclase ◽  
Natriuretic Peptides ◽  
Soluble Guanylate Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Pharmacological Intervention ◽  
First Line ◽  
Phosphodiesterase Type ◽  
Activity Mechanism

For years, guanylate cyclase seemed to be homogenic and tissue nonspecific enzyme; however, in the last few years, in light of preclinical and clinical trials, it became an interesting target for pharmacological intervention. There are several possible options leading to an increase in cyclic guanosine monophosphate concentrations. The first one is related to the uses of analogues of natriuretic peptides. The second is related to increasing levels of natriuretic peptides by the inhibition of degradation. The third leads to an increase in cyclic guanosine monophosphate concentration by the inhibition of its degradation by the inhibition of phosphodiesterase type 5. The last option involves increasing the concentration of cyclic guanosine monophosphate by the additional direct activation of soluble guanylate cyclase. Treatment based on the modulation of guanylate cyclase function is one of the most promising technologies in pharmacology. Pharmacological intervention is stable, effective and safe. Especially interesting is the role of stimulators and activators of soluble guanylate cyclase, which are able to increase the enzymatic activity to generate cyclic guanosine monophosphate independently of nitric oxide. Moreover, most of these agents are effective in chronic treatment in heart failure patients and pulmonary hypertension, and have potential to be a first line option.

Discovery of CYR715: A novel carboxylic acid-containing soluble guanylate cyclase stimulator

2021 ◽  
pp. 127886
Author(s):  
Glen R. Rennie ◽  
Timothy C. Barden ◽  
Sylvie G. Bernier ◽  
Andrew Carvalho ◽  
Renee Deming ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Soluble Guanylate Cyclase Stimulator
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