PPAR agonist 8
PPAR agonist 8 is an orally active pan-PPAR agonist, with KD values of 0.576 μM, 2.06 μM and 1.45 μM for PPARα, PPARγ and PPARδ, respectively. PPAR agonist 8 upregulates the expression of ATP-binding cassette transporter A1 (ABCA1) and promotes cholesterol efflux. PPAR agonist 8 reduces plasma cholesterol levels, decreases cholesterol accumulation in the liver and cholesterol deposition in pancreatic islets, regulates glucose and lipid metabolism, and causes no side effects of weight gain and obesity. PPAR agonist 8 can be used in the research of type 2 diabetes, hepatic steatosis and pancreatic islet dysfunction.
For research use only. We do not sell to patients.
- CAS No.: 1031072-40-8
- Formula: C13H10N2O4
- Molecular Weight:258.23
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
PPARα 0.576 μM (Kd) |
PPARγ 2.06 μM (Kd) |
PPARδ 1.45 μM (Kd) |
In Vitro
PPAR agonist 8 (Compound 15a) potently and evenly activates hPPARα, hPPARγ and hPPARδ in HepG2 cells, with EC50 values of 6.94 μM, 13.87 μM and 3.83 μM, respectively[1].
PPAR agonist 8 (24 h) potently upregulates the activity of the ABCA1 promoter in HepG2 cells, with an EC50 of 4.27 μM and a maximum activation rate of 431% relative to DMSO[1].
PPAR agonist 8 (10 μM; 40 min) enhances glucose-stimulated insulin secretion in INS-1 cells in an ABCA1-dependent manner[1].
PPAR agonist 8 (1-10 μM; 7 days) does not significantly promote adipogenic differentiation or lipid accumulation in 3T3-L1 preadipocytes, thus avoiding the adipogenic side effects of selective PPARγ agonists[1].
PPAR agonist 8 (30 μM) exhibits only 20.72% inhibition of the hERG K+ channel, indicating a low risk of QT interval prolongation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:KKAy mice (male, 6-week-old, high fat and high glucose diet-induced T2DM model)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 24 days
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Result:Restored body weight to near-normal control levels, avoiding weight gain associated with RGZ treatment.
Markedly decreased plasma total cholesterol (TC) and triglyceride (TG) levels.
Surpassed RGZ in reducing fasting blood glucose and homeostatic model assessment of insulin resistance (HOMA-IR) levels.
Significantly improved oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) area under the curve (AUC) values.
Reduced liver weight, liver weight-to-body weight ratio, hepatic TC and TG accumulation, and cholesterol deposition in liver tissue; promoted fecal cholesterol excretion; decreased plasma alanine transaminase (ALT) levels.
Ameliorated hepatic steatosis and lipid accumulation as shown by H&E and Oil Red O staining.
Upregulated hepatic mRNA expression of glucose metabolism-related genes (glucokinase (Gck), glucose transporter 2 (Glut2), insulin receptor substrate 1 (Irs1)) and cholesterol efflux genes (ATP binding cassette subfamily A member 1 (Abca1), ATP binding cassette subfamily G member 5 (Abcg5), ATP binding cassette subfamily G member 8 (Abcg8)); downregulated hepatic mRNA expression of gluconeogenic genes (glucose-6-phosphatase (G6pc), fructose-Bisphosphatase 2 (Fbp2)), cholesterol synthesis gene (3-hydroxy-3-methylglutaryl-CoA synthase 1 (Hmgcs1)), adipogenesis-related factors (cluster of differentiation 36 (Cd36), stearoyl-CoA desaturase (Scd1), ELOVL fatty acid elongase 6 (Elovl6), Pparγ1), and inflammatory cytokines (Il1α, Il1β); increased hepatic mRNA expression of Pparα and Pparδ.
Ameliorated islet hypertrophy, disorganized islet cell arrangement, and islet cholesterol accumulation; increased islet ABCA1 expression and insulin secretion.
Reduced epididymal and subcutaneous white adipose tissue (eWAT, sWAT) mass, avoided adipogenic side effects of RGZ, and ameliorated adipocyte hypertrophy and adipose tissue macrophage infiltration.
Chemical Information
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CAS No. 1031072-40-8
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Molecular Weight 258.23
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Formula C13H10N2O4
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SMILES
O=C(NC1=NC=CC=C1O)C2=CC(OCO3)=C3C=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Human Islet Cell Culture
The method of preserving islets in vitro, with purified reduced immunogenicity. The steps are islet isolation, islet cell purification, in vitro determination of islet function and islet cell culture.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
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Liver Histomorphometry
Liver histomorphometry is a quantitative histological approach used to measure structural alterations in hepatic tissue, including parenchymal loss, steatosis, fibrosis, and vascular remodeling, by combining stained tissue section analysis with stereological or computerized image-based measurements. Classical morphometric frameworks quantify volume fractions of liver compartments and fibrotic regions using systematic sampling and image analysis, enabling objective comparison of pathological changes across experimental groups. These approaches are widely applied in liver cirrhosis and fibrosis studies to reduce subjectivity in histological scoring and improve reproducibility of tissue evaluation. Recent methodological advances integrate automated image analysis and radiomics-based extraction of histological features from standard liver stains (e. g. , H&E and fibrotic stains), enabling quantitative correlation between morphometric features and fibrosis stages in non-alcoholic fatty live
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)