Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease.
cGMP
cardioprotective
nitric oxide
olinciguat
renoprotective
soluble guanylate cyclase
vascular inflammation
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
12
2019
accepted:
19
03
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
24
4
2020
Statut:
epublish
Résumé
Nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic 3',5' GMP (cGMP) signaling plays a central role in regulation of diverse processes including smooth muscle relaxation, inflammation, and fibrosis. sGC is activated by the short-lived physiologic mediator NO. sGC stimulators are small-molecule compounds that directly bind to sGC to enhance NO-mediated cGMP signaling. Olinciguat, (R)-3,3,3-trifluoro-2-(((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-yl)amino)methyl)-2-hydroxypropanamide, is a new sGC stimulator currently in Phase 2 clinical development. To understand the potential clinical utility of olinciguat, we studied its pharmacokinetics, tissue distribution, and pharmacologic effects in preclinical models. Olinciguat relaxed human vascular smooth muscle and was a potent inhibitor of vascular smooth muscle proliferation
Identifiants
pubmed: 32322204
doi: 10.3389/fphar.2020.00419
pmc: PMC7156612
doi:
Types de publication
Journal Article
Langues
eng
Pagination
419Informations de copyright
Copyright © 2020 Zimmer, Shea, Tobin, Tchernychev, Germano, Sykes, Banijamali, Jacobson, Bernier, Sarno, Carvalho, Chien, Graul, Buys, Jones, Wakefield, Price, Chickering, Milne, Currie and Masferrer.
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