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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

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

Author(s): Sijia Xiao, Qianbin Li*, Liqing Hu, Zutao Yu, Jie Yang, Qi Chang, Zhuo Chen and Gaoyun Hu

Volume 19 , Issue 18 , 2019

Page: [1544 - 1557] Pages: 14

DOI: 10.2174/1389557519666190730110600

Price: $65


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.

Keywords: Soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), NO-sGC-cGMP pathway, sGC stimulators and activators, heart failure, vasorelaxation.

Graphical Abstract
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