Peter Germano
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View article: Zagociguat prevented stressor-induced neuromuscular dysfunction, improved mitochondrial physiology, and increased exercise capacity in diverse mitochondrial respiratory chain disease zebrafish models.
Zagociguat prevented stressor-induced neuromuscular dysfunction, improved mitochondrial physiology, and increased exercise capacity in diverse mitochondrial respiratory chain disease zebrafish models. Open
Preclinical evaluation of zag demonstrated its safety, significant protection of neuromuscular dysfunction and/or acute RC stressor-induced decompensation, and improved mitochondrial physiology across multiple different genetic and/or phar…
View article: <scp>FAAH</scp> inhibitor <scp>URB597</scp> shows anti‐hyperalgesic action and increases brain and intestinal tissues fatty acid amides in a model of <scp>CRF<sub>1</sub></scp> agonist mediated visceral hypersensitivity in male rats
<span>FAAH</span> inhibitor <span>URB597</span> shows anti‐hyperalgesic action and increases brain and intestinal tissues fatty acid amides in a model of <span>CRF<sub>1</sub></span> agonist mediated visceral hypersensitivity in male rats Open
Background and Aims The endocannabinoid (eCB) system includes ligands (anandamide and 2‐arachidonoyl glycerol, 2‐AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the b…
View article: Beneficial Metabolic Effects of Praliciguat, a Soluble Guanylate Cyclase Stimulator, in a Mouse Diet-Induced Obesity Model
Beneficial Metabolic Effects of Praliciguat, a Soluble Guanylate Cyclase Stimulator, in a Mouse Diet-Induced Obesity Model Open
Praliciguat is a soluble guanylate cyclase stimulator that elicits hemodynamic, anti-inflammatory, and antifibrotic effects in preclinical models of metabolic dysfunction. We assessed the metabolic effects of praliciguat in a mouse diet-in…
View article: The CNS-Penetrant Soluble Guanylate Cyclase Stimulator CY6463 Reveals its Therapeutic Potential in Neurodegenerative Diseases
The CNS-Penetrant Soluble Guanylate Cyclase Stimulator CY6463 Reveals its Therapeutic Potential in Neurodegenerative Diseases Open
Effective treatments for neurodegenerative diseases remain elusive and are critically needed since the burden of these diseases increases across an aging global population. Nitric oxide (NO) is a gasotransmitter that binds to soluble guany…
View article: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease
Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease Open
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…
View article: Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical‐stage soluble guanylate cyclase stimulator in rats
Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical‐stage soluble guanylate cyclase stimulator in rats Open
The pharmacokinetics (PK), metabolism, excretion, mass balance, and tissue distribution of [ 14 C]praliciguat were evaluated following oral administration of a 3‐mg/kg dose in Sprague‐Dawley rats and in a quantitative whole‐body autoradiog…
View article: Meeting abstracts from the 9th International Conference on cGMP: Generators, Effectors and Therapeutic Implications
Meeting abstracts from the 9th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Open
Introduction:The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signaling pathway plays a fundamental role in modulating diverse physiological processes within the central nervous system (CNS) including blood flow, inflammation, ne…
View article: Pharmacological Characterization of IW-1973, a Novel Soluble Guanylate Cyclase Stimulator with Extensive Tissue Distribution, Antihypertensive, Anti-Inflammatory, and Antifibrotic Effects in Preclinical Models of Disease
Pharmacological Characterization of IW-1973, a Novel Soluble Guanylate Cyclase Stimulator with Extensive Tissue Distribution, Antihypertensive, Anti-Inflammatory, and Antifibrotic Effects in Preclinical Models of Disease Open
Soluble guanylate cyclase (sGC), a key signal-transduction enzyme, increases the conversion of guanosine-5'-triphosphate to cGMP upon binding of nitric oxide (NO). Endothelial dysfunction and/or reduced NO signaling have been implicated in…
View article: Discovery of IWP-051, a Novel Orally Bioavailable sGC Stimulator with Once-Daily Dosing Potential in Humans
Discovery of IWP-051, a Novel Orally Bioavailable sGC Stimulator with Once-Daily Dosing Potential in Humans Open
In recent years, soluble guanylate cyclase (sGC, EC 4.6.1.2) has emerged as an attractive therapeutic target for treating cardiovascular diseases and diseases associated with fibrosis and end-organ failure. Herein, we describe our design a…
View article: Concomitant administration of sGC stimulators with common classes of anti-hypertensive agents results in increased efficacy in spontaneously hypertensive rats
Concomitant administration of sGC stimulators with common classes of anti-hypertensive agents results in increased efficacy in spontaneously hypertensive rats Open
Background Soluble guanylate cyclase (sGC) stimulators demonstrate smooth muscle relaxation and vasodilation via the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway. A novel class of sGC stimulators, the pyrazole-pyrimi…