Kylo-0603
Kylo-0603 is an orally active thyroid hormone receptor β (THR-β) agonist with an EC50 of 31.07 nM against human targets, and it exhibits much higher selectivity for THR-β than for THR-α. Kylo-0603 enables hepatocyte-targeted delivery via GalNAc modification. Kylo-0603 reduces serum cholesterol and low-density lipoprotein cholesterol levels. Kylo-0603 alleviates hepatic steatosis, inflammatory responses, hepatocyte ballooning, and non-alcoholic steatohepatitis activity scores. Kylo-0603 inhibits the progression of hepatic fibrosis. Kylo-0603 can be used for research on metabolic dysfunction-associated steatohepatitis (MASH).
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- CAS No.: 2661053-09-2
- Formule: C81H134N8O28
- Masse moléculaire:1667.97
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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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Help & FAQs
Activité biologique
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THR-β 31.07 nM (EC50) |
Kylo-0603 (40-400 μM) acts as a human THR-β-selective agonist with an 8.2-fold greater relative selectivity for THR-β over THR-α, exhibiting EC50 values of 31 nM for THR-β and 124 nM for THR-α in a cell-free TR-FRET assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Kylo-0603 (0.1-10 mg/kg; p.o.; once daily; for 8 weeks) dose-dependently improves MASH pathological manifestations, alleviates hepatic fibrosis and steatosis, restores normal thyroid hormone levels, and regulates the expression of genes related to lipid metabolism, inflammation and fibrosis in HFD+CCl4-induced MASH mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 5 weeks old, high-fat diet induced)[1]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 10 weeks
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Result:Reduced body weights by 0.8%, 4.8%, 3.8%, 13.1%, and 15.8% respectively compared to the HFD group.
Reduced fat content by 8.96%, 9.16%, 14.07%, 26.15%, and 44.35% respectively compared to the HFD group.
Increased lean mass percentage by 5.32%, 10.95%, 13.52%, 21.94%, and 37.91% respectively compared to the HFD group.
Reduced serum cholesterol by 52.0% and 64.5% at 3 mg/kg and 10 mg/kg doses respectively after 2 weeks of treatment compared to the HFD group.
Reduced LDL-C by 84.0% and 85.8% at 3 mg/kg and 10 mg/kg doses respectively after 2 weeks of treatment compared to the HFD group.
Reduced serum cholesterol by 30.6%, 35.9%, 47.9%, 53.9%, and 69.2% respectively after 10 weeks of treatment compared to the HFD group.
Reduced LDL-C by 58.0%, 72.7%, 81.8%, 79.7%, and 88.2% respectively after 10 weeks of treatment compared to the HFD group.
Reduced liver triglyceride content by up to 36.4% at the 3 mg/kg dose compared to the HFD group.
Did not significantly affect liver cholesterol content compared to the HFD group.
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Animal Model:C57BL/6J (male, 5 weeks old, high-fat diet plus CCl4 induced)[1]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 8 weeks
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Result:Reduced body weights by 0.8% to 15.8% in a dose-dependent manner compared to the HFD+CCl4+vehicle group.
Reduced serum cholesterol and LDL-C in a dose-dependent manner compared to the HFD+CCl4+vehicle group.
Reduced serum ALT by 73.8% and AST by 76.3% at the 3 mg/kg dose compared to the HFD+CCl4+vehicle group.
Increased thyroid hormone levels (T3, fT3, T4, fT4) and decreased TSH in a dose-dependent manner compared to the HFD+CCl4+vehicle group.
Reduced steatosis scores by 1.5 points and 1.3 points) at 3 mg/kg and 10 mg/kg doses respectively compared to the HFD+CCl4+vehicle group.
Reduced inflammation scores by 1.5 points and 1.8 points at 3 mg/kg and 10 mg/kg doses respectively compared to the HFD+CCl4+vehicle group.
Reduced ballooning scores by 0.7 points and 0.8 points at 3 mg/kg and 10 mg/kg doses respectively compared to the HFD+CCl4+vehicle group.
Reduced NASH activity score (NAS) by 3.5 points and 3.7 points at 3 mg/kg and 10 mg/kg doses respectively compared to the HFD+CCl4+vehicle group.
Reduced fibrosis scores by 0.6 points at both 3 mg/kg and 10 mg/kg doses compared to the HFD+CCl4+vehicle group.
Reduced liver fibrosis percentage from 4.36% to 2.92%, 2.12%, 2.16%, 2.03%, and 1.25% respectively compared to the HFD+CCl4+vehicle group.
Reduced steatosis area from 21.66% to 5.07%, 4.39%, 4.19%, 2.22%, and 1.86% respectively compared to the HFD+CCl4+vehicle group.
Upregulated Dio1, Thrsp, Me1, and LDL-R in a dose-dependent manner compared to the HFD+CCl4+vehicle group.
Downregulated inflammatory genes (Tnfrsf1a, IL6, IL17rb, IL17ra) and collagen synthesis genes (Col6a3, Col4a5, Col1a2, Col4a2, Tgfb2, Col4a1, Col1a1) in a dose-dependent manner compared to the HFD+CCl4+vehicle group.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2661053-09-2
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Masse moléculaire 1667.97
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Formule C81H134N8O28
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SMILES
O=C(CCOCC(COCCC(NCCCCCCO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1NC(C)=O)=O)(NC(CCCCCNC(COC2=CC(C)=C(CC3=CC(C(C)C)=C(O)C=C3)C(C)=C2)=O)=O)COCCC(NCCCCCCO[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4NC(C)=O)=O)NCCCCCCO[C@@H]5O[C@H](CO)[C@H](O)[C@H](O)[C@H]5NC(C)=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
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Fiche technique (277 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Kylo-0603 Related Classifications
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