Resmetirom

Resmetirom (MGL-3196) is a highly selective and orally active thyroid hormone receptor β (THR-β) agonist with an EC₅₀ value of 0.21 μM. Resmetirom can be used for the study of noncirrhotic nonalcoholic steatohepatitis^[1]. IC50 & Target:EC50: 0.21 μM (THR-β)^[1] In Vitro:Resmetirom (MGL-3196) is 28-fold selective for THR-β (EC₅₀=0.21 μM) over THR-α (EC₅₀=3.74 μM ) in a functional assay. Resmetirom (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]. 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].