TLC-2716
TLC-2716 is an orally available, gut- and liver-restricted inhibitor against LXRα and LXRβ, with EC50 values of 7 nM and 15 nM, respectively. TLC-2716 represses LXRα/β transcriptional activity, downregulates genes involved in lipogenesis, lipid absorption and lipoprotein metabolism, and preserves peripheral reverse cholesterol transport. TLC-2716 reduces lipid accumulation, suppresses inflammation and fibrotic gene expression, enhances triglyceride-rich lipoprotein clearance, and improves glucose homeostasis and insulin sensitivity. TLC-2716 lowers serum and hepatic triglycerides, plasma cholesterol and other atherogenic lipid profiles in experimental models and humanized liver mice. TLC-2716 can be used for the research of dyslipidemia and related cardiometabolic disorders.
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- CAS No.: 2408041-54-1
- Formule: C38H22ClF3N4O5S
- Masse moléculaire:739.12
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
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LXRα 7 nM (EC50) |
LXRβ 15 nM (EC50) |
TLC-2716 (1 h at 4 °C) binds to recombinant human LXRα (EC50 = 7 nM) and LXRβ (EC50 = 15 nM) in a biochemical binding assay[1].
TLC-2716 (16 h) induces NCOR recruitment to LXRα and LXRβ with EC50 values of 8 nM and 11 nM in HEK293 mammalian two‑hybrid assays, and inhibits ABCA1 and SREBP1c reporter activities with IC50 values of 15 nM and 7 nM in HT‑29 and HepG2 cells, respectively[1].
TLC-2716 (5 days) dose-dependently reduces intracellular triglyceride accumulation in primary human Upcyte hepatocytes with an EC50 of 289 nM[1].
In steatotic human liver organoids, TLC-2716 (500 nM-5 μM; 3 days) dose-dependently reduces intracellular lipid content and suppresses expression of LXR-associated, lipid metabolism, inflammation, and fibrosis-related genes, with enhanced effects in GCKRTT organoids[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
TLC-2716 (0.1-15 mg/kg; p.o.; daily) reduces dyslipidemia-related endpoints and improves glucose homeostasis in ZDF rats without impairing liver function[1].
TLC-2716 (0.1-1 mg/kg; p.o.; daily; 21 days) reduces hepatic DNL gene expression, liver TG, and plasma TG and TC in high-fat diet-fed SD rats without impairing liver function[1].
TLC-2716 (1 mg/kg; p.o.; daily; 8 days) reduces hepatic expression of lipid metabolism genes and trends to reduce liver TG in human liver chimeric mice[1].
TLC-2716 (15-120 mg/kg; oral gavage; once daily; 26 weeks) reduces plasma TG and TC in lean CD-1 mice without causing observable adverse effects[1].
TLC-2716 (1-15 mg/kg; oral gavage; once daily; 28 days) reduces plasma TG and TC in cynomolgus monkeys without causing observable adverse effects[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 18 weeks old, diet-induced obese via 14 weeks high-fat diet)[1]
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Dosage:0.3 mg/kg; 1 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Dose-dependently reduced hepatic expression of de novo lipogenesis (DNL) genes including Scd1, Fasn, Srebp1c and Acaca.
Decreased liver triglyceride (TG) content as well as area under the curve (AUC) values for plasma TG and total cholesterol (TC) at 1 mg/kg, with milder reductions observed at 0.3 mg/kg.
Maintained comparable plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels versus vehicle treatment.
Dose-dependently downregulated ileal Srebp1c expression.
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Animal Model:Zucker diabetic fatty (ZDF) (male, 6-7 weeks old, obese fa/fa)[1]
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Dosage:0.1 mg/kg; 1 mg/kg; 15 mg/kg
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Administration:p.o.; daily; 14 days (0.1, 1 mg/kg); p.o.; daily; 28 days (15 mg/kg)
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Result:Reduced hepatic DNL gene expression, liver TG content, and AUC for plasma TG and TC at 0.1 and 1 mg/kg.
Reduced fasting plasma glucose by approximately 56% and lowered hepatic Angptl3 expression and plasma ANGPTL3 levels at 15 mg/kg.
Remained unchanged plasma ALT and AST levels relative to vehicle.
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Animal Model:Sprague-Dawley (SD) (male, 6-7 weeks old, high-fat diet-induced obese)[1]
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Dosage:0.1 mg/kg; 1 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Reduced hepatic DNL gene expression, liver TG content, and AUC for plasma TG and TC at both doses.
Remained unchanged plasma ALT and AST levels relative to vehicle.
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Animal Model:PXB (male, humanized liver chimeric)[1]
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Dosage:1 mg/kg
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Administration:oral gavage; once daily; 8 days
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Result:Trended to reduce liver TG content.
Reduced hepatic expression of cholesterol synthesis gene HMGCR, lipid clearance gene ANGPTL3, and de novo lipogenesis genes SREBP1C, FASN, ACACA, SCD1.
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Animal Model:CD-1 (male and female, lean)[1]
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Dosage:15 mg/kg; 60 mg/kg; 120 mg/kg
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Administration:p.o.; daily; 182 days
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Result:Reduced plasma TG and TC in both male and female mice at all doses.
Observed no adverse clinical observations, liver biochemistry changes, or histopathological signs of liver injury at any dose.
Chemical Information
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CAS No. 2408041-54-1
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Masse moléculaire 739.12
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Formule C38H22ClF3N4O5S
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SMILES
OC(CNC(C1=CC=C(C2=CC(C3=C(C4=C(C#N)C=CC=C4C#N)C5=CC(F)=CC=C5N3S(C6=CC=C(C(F)F)C=C6)(=O)=O)=CC=C2)C(Cl)=C1)=O)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TLC-2716 Related Classifications
HY-182014 Related Classifications
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