| Description |
MGL-3196 is a highly selective thyroid hormone receptor β (THR-β) agonist with an EC50 value of 0.21 μM.
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| Related Catalog |
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| Target |
EC50: 0.21 μM (THR-β)[1]
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| In Vitro |
MGL-3196 is 28-fold selective for THR-β (EC50=0.21 μM) over THR-α (EC50=3.74 μM ) in a functional assay. MGL-3196 shows an IC20 of roughly 30 μM for blockage of the hERG channel. The IC50 for CYP3A4/5 and for CYP2C19 is >50 μM, and there is only weak inhibition (roughly 22 μM) of CYP2C9[1].
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| In Vivo |
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 MGL-3196 given orally to DIO mice[1].In animals treated with 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 MGL-3196 treated animals[1].
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| Animal Admin |
Rats: 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: 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 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].
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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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