| Identification | Back Directory | [Name]
MGL-3196 | [CAS]
920509-32-6 | [Synonyms]
VIA3196
CS-2429
VIA-3196
MGL-3196
Resmetirom
Resmetirom(MGL-3196)
MGL-3196(Resmetirom)
Resmetirom (MGL-3196,VIA-3196)
MGL-3196; MGL 3196; MGL3196; VIA-3196; VIA3196; VIA-3196
2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile
2-[3,5-Dichloro-4-[[1,6-dihydro-5-(1-methylethyl)-6-oxo-3-pyridazinyl]oxy]phenyl]-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carbonitrile
1,2,4-Triazine-6-carbonitrile, 2-[3,5-dichloro-4-[[1,6-dihydro-5-(1-methylethyl)-6-oxo-3-pyridazinyl]oxy]phenyl]-2,3,4,5-tetrahydro-3,5-dioxo- | [Molecular Formula]
C17H12Cl2N6O4 | [MDL Number]
MFCD26142653 | [MOL File]
920509-32-6.mol | [Molecular Weight]
435.22 |
| Chemical Properties | Back Directory | [density ]
1.65±0.1 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,Store in freezer, under -20°C | [solubility ]
DMSO:59.0(Max Conc. mg/mL);135.56(Max Conc. mM) | [form ]
A crystalline solid | [pka]
3.96±0.40(Predicted) | [color ]
Yellow to orange | [InChI]
InChI=1S/C17H12Cl2N6O4/c1-7(2)9-5-13(22-23-15(9)26)29-14-10(18)3-8(4-11(14)19)25-17(28)21-16(27)12(6-20)24-25/h3-5,7H,1-2H3,(H,23,26)(H,21,27,28) | [InChIKey]
FDBYIYFVSAHJLY-UHFFFAOYSA-N | [SMILES]
N1=C(C#N)C(=O)NC(=O)N1C1=CC(Cl)=C(OC2=NNC(=O)C(C(C)C)=C2)C(Cl)=C1 |
| Hazard Information | Back Directory | [Description]
MGL-3196 is an agonist of thyroid hormone receptor β (TRβ; EC50s = 0.21 and 3.74 μM for TRβ and TRα, respectively).1 It also inhibits ether-a-go-go-related gene (ERG) potassium channels (IC50 = 30 μM). MGL-3196 is a liver-directed compound, with a liver to plasma ratio of 8:1 in mice with diet-induced obesity (DIO), which reduces the likelihood of adverse effects from systemic exposure. It does not affect the expression of α-myosin heavy chain (α-MHC) in a rat model of hypothyroidism, an effect mediated by TRα, indicating low potential for cardiac adverse effects. MGL-3196 lowers non-HDL cholesterol and liver triglycerides without affecting thyroid stimulating hormone (Tsh) levels in rat and rabbit models of hypercholesterolemia. It also lowers plasma glucose levels and improves insulin sensitivity in DIO mice. Formulations containing MGL-3196 are in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) and familial hypercholesterolemia. | [Uses]
Resmetirom (MGL-3196) is a liver-directed, orally active, selective thyroid hormone receptor-beta agonist. It works by blocking the formation of fat in the liver and can be used to treat non-alcoholic steatohepatitis (NASH). | [Indications]
Resmetirom is an oral thyroid hormone receptor-β (THR-β) agonist being developed by Madrigal Pharmaceuticals, Inc. to target the key underlying causes of metabolic dysfunction associated steatohepatitis (MASH) [previously known as nonalcoholic steatohepatitis (NASH)]. In March 2024, resmetirom was approved for use (under accelerated approval) in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in the USA. Currently, Resmetirom has been approved by the FDA for the treatment of adult patients with non-alcoholic steatohepatitis (NASH). | [Brand name]
Rezdiffra | [Mechanism of action]
Resmetirom is a selective thyroid hormone receptor β (THRβ) agonist that primarily acts on hepatic lipid metabolism. In metabolic and alcoholic steatohepatitis (MASH), it exerts its effects by stimulating THRβ signalling, enhancing mitochondrial β-oxidation and reducing lipid synthesis. It also improves inflammatory and fibrotic conditions[2]. | [Side effects]
Common side effects of Resmetirom include: diarrhea, nausea, itching, stomachache, vomiting, dizziness and constipation. Among them, diarrhea and nausea are the most common side effects, often seen in the early stage of treatment, ranging from mild to moderate, and lasting for 3 to 4 weeks. In severe cases, it can lead to liver damage and gallstones or inflammation of the gallbladder/pancreas. | [in vivo]
Resmetirom (MGL-3196) exhibits good exposures and reasonable oral bioavailability in rats. The volume of distribution and clearance are both low. Dose proportional increases in exposure are observed for a suspension of Resmetirom (MGL-3196) given orally to DIO mice[1].In animals treated with Resmetirom (MGL-3196) there is a reduction in cholesterol and in liver size, which is secondary to reduction of liver TG. There is no effect on bone mineral density (BMD) or heart or kidney size in Resmetirom (MGL-3196) treated animals[1]. | [References]
[1] MARTHA J. KELLY*. 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]. Journal of Medicinal Chemistry, 2014, 57 10: 3912-3923. DOI: 10.1021/jm4019299 |
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