A5052381405- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Cholesterol and Lipid Metabolism
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Biochemical and Molecular Research
- Neuroscience and Neuropharmacology Research
- Diet, Metabolism, and Disease
- Inflammatory mediators and NSAID effects
- Liver Disease Diagnosis and Treatment
- Natural Products and Biological Research
- Plant biochemistry and biosynthesis
- Adipose Tissue and Metabolism
- Pharmacological Effects of Natural Compounds
Daiichi-Sankyo (Japan)
2009-2019
Daiichi Sankyo (Germany)
2009-2015
Daiichi-Sankyo (South Korea)
2013
Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the biosynthesis of monounsaturated fatty acids, and their abnormality is possibly responsible for obesity, insulin resistance, hepatic steatosis nonalcoholic steatohepatitis (NASH). A novel SCD-1 inhibitor, N-(2-hydroxy-2-phenylethyl)-6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxamide, has been obtained. The compound inhibited liver activity increased triglyceride accumulation in mice fed with non-fat, high-sucrose diets. In order to...
GPR40 is a G protein-coupled receptor that predominantly expressed in pancreatic β-cells. agonists stimulate insulin secretion the presence of high glucose concentration. On basis this mechanism, are possible novel secretagogues with reduced or no risk hypoglycemia. The improvement vitro activity and metabolic stability compound 1 led to discovery 13, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, as potent orally available agonist....
We show an efficient method to identify molecular targets of small compounds by affinity purification and mass spectrometry. Binding proteins were isolated from target cell lysate using columns, which immobilized the active inactive compounds. All bound these columns eluted digestion trypsin then identified The specific binding compound, a candidate for targets, determined subtracting in compound-immobilized column that column. This was applied identification D942, furancarboxylic acid...
Peroxisome proliferator-activated receptor γ (PPARγ; NR1C3) is known as a key regulator of adipocytogenesis and the molecular target thiazolidinediones (TZDs), also antidiabetic agents. Despite clinical benefits TZDs, their use often associated with adverse effects including peripheral edema, congestive heart failure, weight gain. Here we report identification characterization non-thiazolidinedione PPARγ partial agonist, Cerco-A, which derivative natural product, (−)-cercosporamide. Cerco-A...
Derivatization efforts were continued to discover backups for a potent selective PPARγ modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As introduction substituents on pyridine did not provide partial agonists, modifications benzimidazole explored intermediate agonists. 4'-Alkoxy substituted benzimidazoles failed show efficacy vivo, whereas 7'-fluoro 3g (DS19161384) was found result robust plasma glucose reductions...