Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Representative olinciguat concentration response in HEK-293 cells, without NO and in the presence of 10 µM DETA.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Concentration Assay

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Concentration response of olinciguat in human subcutaneous resistance arteries pre-contracted with U46619 (100 nM). Percent relaxation is relative to the U46619-mediated contraction. Each data point represents the mean from assays in tissues from n=3 human donors, error bars represent the SEM.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Concentration Assay

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Effect of olinciguat on vascular smooth muscle cell proliferation. Concentration response of tadalafil alone (TAD), olinciguat alone (OLI), and olinciguat in the presence of 1 µM tadalafil (OLI + TAD1) on proliferation of VSMC from rat aorta, as measured by cellular 3 H thymidine incorporation in response to 5% FBS. All assays included 10 µM DETA. Data are normalized to FBS control. Each data point represents the mean from n=3 independent assays, error bars represent the SEM. The IC 50 s for olinciguat alone vs in the presence of 1 µM tadalafil were significantly different from each other (p=2.4E-07).

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Concentration Assay, Control

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Pharmacokinetics of olinciguat in female and male Sprague Dawley rats.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Drug discovery

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Effect of olinciguat dose on mean arterial pressure, measured by telemetry in freely moving normotensive Wistar and spontaneously hypertensive rats (SHR). Data are shown for baseline (−24 h to 0 h) and the first 3 days of dosing QD by oral gavage. Timing of dosing is indicated by dashed vertical lines at 0, 24, and 48 h. Data are plotted as means over time (n=6 per group), for simplicity, no error bars are included. Tx, treatment. For each treatment group, MAP measurements that were significantly (p < 0.05) lower than vehicle-treated rats are indicated by filled rectangles in the corresponding color.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Effect of olinciguat on blood pressure, cardiac weights, lung weights, and NT-proBNP in Dahl salt-sensitive rat. (A) Mean arterial pressure vs time profiles in NS and HS controls, and HS rats treated with olinciguat 10 mg/kg (OLI10). HS groups were put on the HS diet starting Week-2. Olinciguat treatment was started on Week 0. Data are plotted as daily average MAP + SEM. (B) Weight of left ventricular wall plus ventricular septum normalized to BW. (C) Lung weight normalized to BW. (D) Plasma NT-proBNP. Data in (B–D) are plotted as mean + SEM, **p < 0.01, ***p < 0.001 vs HS control. For the OLI10 group, MAP measurements that were significantly (p < 0.05) lower than vehicle-treated rats are indicated by filled rectangles.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Clinical Proteomics, Control

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Effect of olinciguat on plasma levels of cellular adhesion molecules in mouse TNFα model of vascular inflammation. *p < 0.05, **p < 0.01, ****p < 0.0001 vs TNFα/vehicle control.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Clinical Proteomics, Control

Journal: Frontiers in Pharmacology

Article Title: Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

doi: 10.3389/fphar.2020.00419

Figure Lengend Snippet: Pharmacological effects of olinciguat in preclinical models.

Article Snippet: Concentrated (10 mM) DMSO stock solutions of olinciguat were diluted to 1 and 10 μM in 2.5 ml of rat (male and female Sprague Dawley) and human plasma.

Techniques: Concentration Assay