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).
For research use only. We do not sell to patients.
- CAS No.: 2661053-09-2
- Formula: C81H134N8O28
- Molecular Weight:1667.97
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
THR-β 31.07 nM (EC50) |
In Vitro
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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.
Clinical Trial
| 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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Molecular Weight 1667.97
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Formula 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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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.
Purity & Documentation
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Data Sheet (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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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Kylo-0603 Related Classifications
HY-172661 Related Classifications
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