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Purity: ≥98%
Resmetirom (formerly known as MGL-3196, MGL 3196) is a novel, highly potent and selective agonist of the thyroid hormone receptor β (THR-β) with EC50 value of 0.21 μM. It is currently in clinical trials for the treatment of Non-alcoholic Steatohepatitis. The beneficial effects of thyroid hormone (TH) on lipid levels are primarily due to its action at the thyroid hormone receptor β (THR-β) in the liver, while adverse effects, including cardiac effects, are mediated by thyroid hormone receptor α (THR-α). MGL-3196 is 28-fold selective for THR-β over THR-α in a functional assay. It also showed outstanding safety in a rat heart model and was efficacious in a preclinical model at doses that showed no impact on the central thyroid axis. In reported studies in healthy volunteers, MGL-3196 exhibited an excellent safety profile and decreased LDL cholesterol (LDL-C) and triglycerides (TG) at once daily oral doses of 50 mg or higher given for 2 weeks.
| ln Vitro |
Compared to THR-α (EC50=3.74 μM), Resmetirom (MGL-3196) exhibits a 28-fold increase in selectivity for THR-β (EC50=0.21 μM). Resmetirom (MGL-3196) is used to inhibit hERG channels and has an IC20 of about 30 μM. The inhibitory effect on CYP2C9 is relatively mild (about 22 μM), whereas the IC50 of CYP3A4/5 and CYP2C19 is >50 μM [1].
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| ln Vivo |
In rats, resmetirom (MGL-3196) showed reasonable oral bioavailability and excellent exposure. There is little distribution volume and little clearing. A dose-proportional increase in exposure was seen in DIO mice after oral administration of Resmetirom (MGL-3196) solution [1]. Due to hepatic TG, cholesterol and liver size were decreased in rats given Resmetirom (MGL-3196). Animals treated with Resmetirom (MGL-3196) showed no change in heart or kidney size, or bone mineral density (BMD) [1].
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| References |
[1]. Kelly MJ, et al. Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a Highly Selective Thyroid Hormone Receptor β agonist in clinical trials for the treatment of dyslipidemia. J Med Chem. 2014 May 22;57(10):3912-23
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| Molecular Formula |
C17H12CL2N6O4
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| Molecular Weight |
435.22
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| CAS # |
920509-32-6
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| SMILES |
N#CC1=NN(C2=CC(Cl)=C(OC(C=C3C(C)C)=NNC3=O)C(Cl)=C2)C(NC1=O)=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.75 mg/mL (8.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.75 mg/mL (8.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3.75 mg/mL (8.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2977 mL | 11.4884 mL | 22.9769 mL | |
| 5 mM | 0.4595 mL | 2.2977 mL | 4.5954 mL | |
| 10 mM | 0.2298 mL | 1.1488 mL | 2.2977 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Model of53(MGL-3196, magenta) bound to THR-β (1N46) with the T3 geometry (cyan) from3GWSsuperimposed. Polar interactions of53in the anion binding site are highlighted.J Med Chem.2014 May 22;57(10):3912-23. |
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(A) 2D description of the binding site for T3 (PDB code3GWS). (B) 2D description of the binding site for the53model (MOE).J Med Chem.2014 May 22;57(10):3912-23. |
Left panel: cardiac α-MHC hnRNA relative levels (arbitrary units) in untreated thyroidectomized rats (control), euthyroid rats, and thyroidectomized rats 6 h after exposure to53dosed intraperitoneally at the specified doses.Right panel: activities of tested compounds relative to full activity (euthyroid or T3-treated) and exposure of the compound 6 h after dose.J Med Chem.2014 May 22;57(10):3912-23. |
Effects of53(MGL-3196) vs T3 on cholesterol and BMD in DIO mice.J Med Chem.2014 May 22;57(10):3912-23. |
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