MGL-3196 - CAS 920509-32-6
Catalog number: B0084-008623
Category: Inhibitor
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MGL-3196 is a first-in-class, orally available, once-daily and liver-directed thyroid hormone receptor (THR) beta-selective agonist. Studies suggest that MGL-3196 has an attractive, differentiated profile as a potential treatment for non-alcoholic steatohepatitis (NASH) and dyslipidemias.
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Catalog Number Size Price Stock Quantity
B0084-008623 250 mg $998 In stock
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Brife Description:
thyroid hormone receptor (THR) beta-selective agonist, NASH, dyslipidemias.
CHEMBL3261331; UNII-RE0V0T1ES0; MGL-3196; MGL 3196; MGL3196; VIA 3196; VIA3196; VIA-3196; Resmetirom.RE0V0T1ES0; 2-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-3,5-dioxo-1,2,4-triazine-6-carbonitrile
potential treatment for non-alcoholic steatohepatitis (NASH) and dyslipidemias
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Madrigal Pharmaceuticals
1.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.
Kelly MJ;Pietranico-Cole S;Larigan JD;Haynes NE;Reynolds CH;Scott N;Vermeulen J;Dvorozniak M;Conde-Knape K;Huang KS;So SS;Thakkar K;Qian Y;Banner B;Mennona F;Danzi S;Klein I;Taub R;Tilley J J Med Chem. 2014 May 22;57(10):3912-23. doi: 10.1021/jm4019299. Epub 2014 Apr 8.
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). A pyridazinone series has been identified that is significantly more THR-β selective than earlier analogues. Optimization of this series by the addition of a cyanoazauracil substituent improved both the potency and selectivity and led to MGL-3196 (53), which is 28-fold selective for THR-β over THR-α in a functional assay. Compound 53 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, 53 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.
2.Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist.
Taub R;Chiang E;Chabot-Blanchet M;Kelly MJ;Reeves RA;Guertin MC;Tardif JC Atherosclerosis. 2013 Oct;230(2):373-80. doi: 10.1016/j.atherosclerosis.2013.07.056. Epub 2013 Aug 21.
MGL-3196 is an oral, liver-targeted selective agonist for the thyroid hormone receptor-β (THR-β) that is being developed for the treatment of dyslipidemia. The safety profile and tolerability of THR-β agonist MGL-3196 was assessed in first-in humans studies, including a single ascending dose study (;NCT01367873;) in which MGL-3196 appeared safe at all doses tested. A two-week multiple dose study was conducted at doses of 5, 20, 50, 80, 100, and 200 mg per day in healthy subjects with mildly elevated low density lipoprotein (LDL) cholesterol (>110 mg/dL) (;NCT01519531;). MGL-3196 was well-tolerated at all doses with no dose-related adverse events or liver enzyme, ECG or vital-sign changes. At the highest dose, there was a reversible reduction of ∼20% in the level of pro-hormone, free thyroxine (free T4) that was significantly different from placebo (p < 0.0001) that may be explained by increased hepatic metabolism of T4. There was no change in thyrotropin (TSH) or triiodothyronine (free T3) or other evidence of central thyroid axis dysfunction at any dose. Doses ranging from 50 to 200 mg demonstrated highly statistically significant reductions relative to placebo of up to: 30% for LDL cholesterol (range, p = 0.
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CAS 920509-32-6 MGL-3196

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