A5031862910- Liver Disease Diagnosis and Treatment
- Diabetes Treatment and Management
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Click Chemistry and Applications
- Diabetes and associated disorders
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- Drug-Induced Hepatotoxicity and Protection
- Pharmacology and Obesity Treatment
- Cannabis and Cannabinoid Research
- Pharmacogenetics and Drug Metabolism
- Mast cells and histamine
- Lipid metabolism and biosynthesis
Pfizer (United States)
2016-2021
Recent studies suggest that excess dietary fructose contributes to metabolic dysfunction by promoting insulin resistance, de novo lipogenesis (DNL), and hepatic steatosis, thereby increasing the risk of obesity, type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH), related comorbidities. Whether this is driven calories contained in or whether catabolism itself uniquely pathogenic remains controversial. We sought test a small molecule inhibitor primary metabolizing enzyme...
Inhibition of DGAT2 reduces steatosis, inflammation, and fibrosis in rodent models NASH liver fat clinical testing.
Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET scans clearance is slow, resulting a carryover effect. We developed method to (1) estimate vivo dissociation constant Kd from studies displaying non-tracer (NTCO) effect and (2) correct NTCO occupancy taking into account plasma its Kd. This was applied study healthy human subjects with histamine H3...
Aims To conduct a dose‐response assessment of the efficacy and safety glucagon receptor antagonist PF‐06291874 in adults with type 2 diabetes (T2DM) using stable doses metformin. Materials Methods This randomized, double‐blind, statin‐stratified, placebo‐controlled, 4‐arm, parallel‐group study was conducted patients T2DM who were receiving background After an 8‐week, non‐metformin oral antidiabetic agent washout period, 206 randomized to placebo or (30, 60 100 mg once daily) for 12 weeks....
The propensity for CYP3A4 induction by 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2<i>H</i>)-yl)acetamide (PF-06282999), an irreversible inactivator of myeloperoxidase, was examined in the present study. Studies using human hepatocytes revealed moderate increases mRNA and midazolam-1′-hydroxylase activity a PF-06282999 dose-dependent fashion. At highest tested concentration 300 <i>μ</i>M, caused maximal enzyme ranging from 56% to 86% 47% t0 72%, respectively,...
Background: PF-06882961 is an oral small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist with efficacy in nonclinical models comparable to injectable peptidic GLP-1R agonists. This randomized, double-blind, placebo-controlled, multiple ascending dose, Phase 1 study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics (PD) of PF–06882961 administered for 28 days patients type 2 diabetes mellitus (T2DM). Methods: A total 98 T2DM taking metformin were 8...