Soluble guanylate cyclase stimulator
Soluble guanylate cyclase (sGC) stimulators are a class of drugs developed to treat heart failure, pulmonary hypertension, and other diseases. The first-in-class medication was riociguat, approved in 2013 for pulmonary hypertension.[1][2] They have also been investigated for hypertension, systemic sclerosis, and sickle cell disease.[3][1]
Background[edit]
In 1998, the role of nitric oxide (NO) in cardiovascular disease received the Nobel Prize in Physiology. Although NO is still used to treat angina, its side effects, potential for tolerance, short duration of action, and narrow therapeutic index limit its therapeutic use.[1][4] PDE5 inhibitors increase NO and are approved for erectile dysfunction, pulmonary arterial hypertension (PAH), and benign prostatic hyperplasia, but they are less effective in patients for whom NO production is suppressed, such as people with diabetes or obesity. Soluble guanylate cyclase is one of the downstream targets of NO, but the stimulators operate independently of it.[1] sGC activators, another experimental class of drugs, may be more effective than stimulators when oxidative stress is high.[1]
The drugs are also considered to possibly have the potential to treat kidney disease, lung fibrosis, scleroderma, and sickle cell disease.[3][1]
List of drugs[edit]
FDA approved[edit]
- Riociguat, approved in 2013 for pulmonary hypertension[1]
- Vericiguat, approved in 2021 for heart failure[5]
Investigational[edit]
- Praliciguat was tried in a phase II trial for heart failure with preserved ejection fraction[6]
- Olinciguat was developed for sickle cell disease but its development was discontinued in 2020.[7]
References[edit]
- ^ a b c d e f g Sandner, Peter (1 July 2018). "From molecules to patients: exploring the therapeutic role of soluble guanylate cyclase stimulators". Biological Chemistry. 399 (7): 679–690. doi:10.1515/hsz-2018-0155. ISSN 1437-4315.
- ^ Sandner, Peter; Vakalopoulos, Alexandros; Hahn, Michael G.; Stasch, Johannes-Peter; Follmann, Markus (4 March 2021). "Soluble guanylate cyclase stimulators and their potential use: a patent review". Expert Opinion on Therapeutic Patents. 31 (3): 203–222. doi:10.1080/13543776.2021.1866538. ISSN 1354-3776.
- ^ a b Stasch, Johannes-Peter; Evgenov, Oleg V. (2013). "Soluble Guanylate Cyclase Stimulators in Pulmonary Hypertension". Pharmacotherapy of Pulmonary Hypertension. Springer. pp. 279–313. ISBN 978-3-642-38664-0.
- ^ Sandner, Peter; Zimmer, Daniel P.; Milne, G. Todd; Follmann, Markus; Hobbs, Adrian; Stasch, Johannes-Peter (2021). "Soluble Guanylate Cyclase Stimulators and Activators". Handbook of Experimental Pharmacology. 264: 355–394. doi:10.1007/164_2018_197. ISSN 0171-2004.
- ^ Markham, Anthony; Duggan, Sean (1 April 2021). "Vericiguat: First Approval". Drugs. 81 (6): 721–726. doi:10.1007/s40265-021-01496-z. ISSN 1179-1950.
- ^ Udelson, James E.; Lewis, Gregory D.; Shah, Sanjiv J.; Zile, Michael R.; Redfield, Margaret M.; Burnett, John; Parker, John; Seferovic, Jelena P.; Wilson, Phebe; Mittleman, Robert S.; Profy, Albert T.; Konstam, Marvin A. (20 October 2020). "Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial". JAMA. 324 (15): 1522. doi:10.1001/jama.2020.16641. PMC 7576408.
- ^ PhD, Joana Carvalho (20 October 2020). "Cyclerion Suspends Development of Olinciguat for Sickle Cell Disease". sicklecellanemianews.com. Retrieved 8 November 2023.
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