MGL-3196

A selective thyroid hormone receptor β agonist with EC₅₀ values of 0.21 and 3.74 µM for THRβ and THRα, respectively. It significantly lowers non-HDL-C and liver TG in hypercholesterolemic rat and rabbit models at doses where there is no effect on TSH levels or the central thyroid axis. It significantly decreased LDL-C by up to 30%, and showed a statistical trend to reduce TG up to 60% in healthy volunteers, at once daily oral dose of 50 mg or higher for 2 weeks. It does not show THR-α mediated gene expression in a rat heart model indicating low potential for cardiac adverse effects. In vitro assays are predictive of lower off target actions. It shows an IC₂₀ of ~30 μM for blockage of the hERG channel and IC₅₀ >50 μM for CYP3A4/5 and CYP2C19. Formulations containing MGL-3196 are in clinical trials for the treatment of dyslipidemia.