Author:
Cottyn S.,Boydens C.,Van de Voorde J.
Abstract
Cytosolic guanylate cyclase as a therapeutic target
The nitric oxide (NO) - soluble guanylyl cyclase (sGC) - cyclic guanosine monophosphate (cGMP) signaling pathway contributes to homeostasis of various systems in an organism. Dysfunction of the system may therefore induce heterogeneous pathologies.
Pharmacological interventions in this signaling pathway using NO donors and phosphodiesterase (PDE) inhibitors have been successful in the past, but still leave room for improvement. This is why the interest in sGC stimulators and activators has been growing. Their NO-independent action increases the activity of sGC, resulting in a higher production of cGMP.
Riociguat is the first sGC stimulator available on the market and is currently used in the treatment of pulmonary hypertension. In addition, other high-potential sGC stimulators or activators are also being tested in several clinical studies.
This article describes the physiological importance of sGC, as well as its potential as a therapeutic target.
Reference57 articles.
1. Binglan YWM, Fumito I, Bloch DB, Warren MZ. Inhaled nitric oxide. Br J Pharmacol 2019; 176: 246-255.
2. 2. Sandner P. From molecules to patients: exploring the therapeutic role of soluble guanylate cyclase stimulators. Biol Chem 2018; 399: 679-690.
3. 3. Lucas KA, Pitari GM, Kazerounian S, Ruiz-stewart I, Park J, Schulz S, et al. Guanylyl cyclases and signaling by cyclic GMP 2000; 52: 375-413.
4. 4. Pyriochou A, Papapetropoulos A. Soluble guanylyl cyclase: more secrets revealed. Cell Signal 2005; 17: 407-413.
5. 5. Kang Y, Liu R, Wu J, Chen L. Structural insights into the mechanism of human soluble guanylate cyclase. Nature Springer US 2019; 574: 206-210.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献