ArticleThe Journal of biological chemistry2018
Discovery of peroxisome proliferator-activated receptor α (PPARα) activators with a ligand-screening system using a human PPARα-expressing cell line.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Cytochrome P450 2E1-dependent hepatic ethanol metabolism induces fatty acid-binding protein 4 and steatosis.Alcoholism, clinical and experimental research · 2022Article
- Exploring compounds to be used as cosmetic agents that activate peroxisome proliferator-activated receptor alpha.International journal of cosmetic science · 2022Article
- Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue.Experimental & molecular medicine · 2021Article
- Chemical Screening of Nuclear Receptor Modulators.International journal of molecular sciences · 2020Review
- Structural Basis for PPARα Activation by 1H-pyrazolo-[3,4-b]pyridine Derivatives.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that belongs to the superfamily of nuclear hormone receptors. PPARα is mainly expressed in the liver, where it activates fatty acid oxidation and lipoprotein metabolism and improves plasma lipid profiles. Therefore, PPARα activators are often used to treat patients with dyslipidemia. To discover additional PPARα activators as potential compounds for use in hypolipidemic drugs, here we established human hepatoblastoma cell lines with luciferase reporter expression from the promoters containing peroxisome proliferator-responsive elements (PPREs) and tetracycline-regulated expression of full-length human PPARα to quantify the effects of chemical ligands on PPARα activity. Using the established cell-based PPARα-activator screening system to screen a library of >12,000 chemical compounds, we identified several hit compounds with basic chemical skeletons different from those of known PPARα agonists. One of the hit compounds, a 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivative we termed compound 3, selectively up-regulated PPARα transcriptional activity, leading to PPARα target gene expression both
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