包装 | 价格(元) |
1mg | 电议 |
5mg | 电议 |
10mg | 电议 |
Animal experiment: | Rats[1]Resmetirom (MGL-3196), compounds 54 and 55 are formulated in 4% DMSO, 15% PEG-400, and 81% of 30% HPBCD in phosphate buffer and are administered intraperitoneally. For MGL-3196 and 54, 4 rats per group are tested at 5, 20, and 37.5 mg/kg. For 55, 3 rats per group are tested at 5 and 15 mg/kg and 4 rats are tested at 50 mg/kg[1]. Mice[1]Six week old C57Bl/6J mice are placed on a high fat diet for 34 weeks. At day 0, 9 mice per group are treated daily doses by gavage with vehicle (2% Klucel LF, 0.1% Tween 80 in water) or 0.3, 1, 3, or 10 mg/kg Resmetirom (MGL-3196) for 23 days. In a parallel study, at day 0, 9 mice per group are treated with daily doses of vehicle (Dulbecco’s phosphate buffered saline, pH adjusted to 9.0 with 1 N NaOH) or 10, 30, or 100 μg/kg T3[1]. |
产品描述 | MGL-3196 is an agonist of thyroid hormone receptor β (TRβ; EC50s = 0.21 and 3.74 uM for TRβ and TRα, respectively). It also inhibits ether-a-go-go-related gene (ERG) potassium channels (IC50 = 30 uM). 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. |