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.
Biological Activity
Description
IC50 & Target
[1]|
THR-β 31.07 nM (EC50) |
In Vitro
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. Further protocols information, click here.
In Vivo
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.
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.
Protocols
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Fibrosis/Collagen Morphometry
Fibrosis and collagen morphometry is based on the quantitative visualization of fibrillar collagen deposition in tissue sections using histochemical stains such as Sirius Red (Picrosirius Red) or Masson's trichrome, followed by image-based or polarization-enhanced analysis to estimate collagen proportional area as a surrogate of extracellular matrix accumulation during fibrotic remodeling. Sirius Red combined with polarized light microscopy enhances detection of collagen fibers due to birefringence properties, enabling more specific visualization of collagen type I and III fibrils compared to conventional bright-field histology, while whole-section or region-restricted digital morphometry reduces field-selection bias in fibrosis assessment. Alternative quantitative approaches include second harmonic generation (SHG) and two-photon excited fluorescence microscopy, which enable label-free detection of fibrillar collagen and have been validated against histological staining and biochemica
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Collagen: Sirius Red Staining
Sirius Red or picrosirius red staining is a histochemical method for visualizing collagen-rich extracellular matrix in tissue sections, and collagen fibers are detected as red-stained structures under bright-field microscopy with enhanced birefringence under polarized light. Picrosirius red is useful for assessing total collagen organization, distribution, and fibrosis burden, but polarized color should not be interpreted as a definitive collagen type I versus type III readout because color is affected by fiber orientation, thickness, and packing.
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Research Protocol for Endocrine Diseases
Endocrine diseases often arise from disrupted hormone production, hormone signaling, or target-tissue responsiveness; for diabetes-focused endocrine disease models, insulin signaling regulates glucose uptake, hepatic glucose output, lipid metabolism, and β-cell compensation. Type 2 diabetes develops through interacting defects in insulin resistance, β-cell dysfunction, adipose inflammation, hepatic glucose overproduction, altered incretin signaling, and ectopic lipid metabolism. A major unresolved question is whether endocrine dysfunction is driven primarily by target-tissue insulin resistance, intrinsic β-cell failure, immune/inflammatory stress, or combined multi-organ failure that differs by disease stage.
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Connective Tissue: Masson's Trichrome/Collagen Trichrome Staining
Masson’s Trichrome (collagen/trichrome staining) is a histological technique that differentially stains tissue compartments using sequential acidic dyes to distinguish collagen from muscle and cytoplasmic components based on dye affinity and tissue permeability differences, enabling visualization of fibrosis and connective tissue architecture in histological sections. The classical formulation typically uses Weigert's iron hematoxylin for nuclear staining, Biebrich scarlet-acid fuchsin for cytoplasm and muscle, and aniline blue (or light green variants) for collagen, producing a characteristic blue/green collagen signal contrasted against red cytoplasm and dark nuclei. The staining principle relies on selective displacement of smaller dye molecules by larger anionic dyes in collagen-rich regions under controlled acidified conditions, which enhances collagen-specific dye retention. This property makes the method widely used for fibrosis assessment in organs such as heart, liver, lung, a
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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
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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)