gw-7647 and Non-alcoholic-Fatty-Liver-Disease

gw-7647 has been researched along with Non-alcoholic-Fatty-Liver-Disease* in 4 studies

Other Studies

4 other study(ies) available for gw-7647 and Non-alcoholic-Fatty-Liver-Disease

ArticleYear
Discovery of new and highly effective quadruple FFA1 and PPARα/γ/δ agonists as potential anti-fatty liver agents.
    European journal of medicinal chemistry, 2022, Feb-05, Volume: 229

    Topics: Animals; Chenodeoxycholic Acid; Drug Discovery; Gene Expression Regulation; Humans; Hypoglycemic Agents; Liver Cirrhosis; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Models, Molecular; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; Protein Binding; Receptors, G-Protein-Coupled; Structure-Activity Relationship

2022
Discovery of (
    Journal of medicinal chemistry, 2022, 07-28, Volume: 65, Issue:14

    A series of fexaramine analogs were synthesized and evaluated to develop an intestine-selective/specific FXR partial agonist. Introduction of both a CN substituent at the C-2 in the biphenyl ring and a fluorine at the C-5 in the aniline ring in fexaramine markedly increased FXR agonistic activity.

    Topics: Acrylates; Animals; Bile Acids and Salts; Esters; Intestines; Liver; Mice; Non-alcoholic Fatty Liver Disease; Rats; Receptors, Cytoplasmic and Nuclear

2022
Discovery of novel modulators for the PPARα (peroxisome proliferator activated receptor α): Potential therapies for nonalcoholic fatty liver disease.
    Bioorganic & medicinal chemistry, 2021, 07-01, Volume: 41

    Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease causing serious liver complications, including nonalcoholic steatohepatitis (NASH). Nuclear receptor PPARα (peroxisome proliferator-activated receptor α) has drawn special attention recently as a potential developmental drug target to treat type-2 diabetes and related diseases due to its unique functions in regulating lipid metabolism, promoting triglyceride oxidation, and suppressing hepatic inflammation, raising interest in PPARα agonists as potential therapies for NAFLD. However, how PPARα coordinates potential treatment of NAFLD and NASH between various metabolic pathways is still obscure. Here, we show that the DY series of novel selective PPARα modulators activate PPARα by up-regulating PPARα target genes directly involved in NAFLD and NASH. The design, synthesis, docking studies, and in vitro and in vivo evaluation of the novel DY series of PPARα agonists are described.

    Topics: Animals; Diet, High-Fat; Female; Gene Expression Regulation; Homeostasis; Lipid Metabolism; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; PPAR alpha; Up-Regulation

2021
PPARα agonist and metformin co-treatment ameliorates NASH in mice induced by a choline-deficient, amino acid-defined diet with 45% fat.
    Scientific reports, 2020, 11-11, Volume: 10, Issue:1

    We explored the beneficial effects of GW7647, a peroxisome proliferator activated receptor α (PPARα) agonist, and metformin, an anti-diabetic drug on an advanced nonalcoholic steatohepatitis (NASH) model in rodents and investigated the possible mechanisms involved. Mice were fed control chow or a choline-deficient L-amino acid-defined diet containing 45% fat (HF-CDAA). The mice fed HF-CDAA diets for 16 weeks were divided into four groups: the no treatment (HF-CDAA), HF-CDAA containing 1000 mg/kg metformin, HF-CDAA containing 10 mg/kg GW7647, and HF-CDAA with both metformin and GW7647 groups. Metformin alone slightly deteriorated the aspartate and alanine aminotransferase (AST/ALT) values, whereas co-treatment with GW7647 and metformin greatly suppressed liver injury and fibrosis via activation of the AMP-activated protein kinase (AMPK) pathway. Further study revealed that co-treatment decreased the expression of inflammatory-, fibrogenesis-, and endoplasmic reticulum (ER) stress-related genes and increased the oxidized nicotinamide adenine dinucleotide (NAD)/reduced nicotinamide adenine dinucleotide (NADH) ratio, suggesting the superiority of co-treatment due to restoration of mitochondrial function. The additive benefits of a PPARα agonist and metformin in a HF-CDAA diet-induced advanced NASH model was firstly demonstrated, possibly through restoration of mitochondrial function and AMPK activation, which finally resulted in suppression of hepatic inflammation, ER stress, then, fibrosis.

    Topics: Alanine Transaminase; Amino Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aspartate Aminotransferases; Butyrates; Choline Deficiency; Diet; Disease Models, Animal; Drug Therapy, Combination; Endoplasmic Reticulum Stress; Fibroblast Growth Factors; Male; Metformin; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phenylurea Compounds; PPAR alpha

2020