Resmetirom (MGL-3196) is a THR-β agonist (EC50=0.21 μM), with high selectivity and oral activity. Resmetirom can be used in the research of non-cirrhotic and non-alcoholic steatohepatitis.

CYP2C9:22 μM, hERG:30 μM, THRβ:0.21 μM (EC50), THRα:3.74 μM (EC50)

METHODS: CYP3A4/5, CYP2C19 and CYP2C9 were treated with Resmetirom to detect the inhibition of cell growth.
RESULTS: The IC50 of ResmetiromCYP3A4/5 and CYP2C19 were both greater than 50 μM, with no growth inhibitory effect. The inhibitory effect on CYP2C9 was relatively weak, and the IC50 was approximately 22 μM. [1]

METHODS: To study the effect of Resmetirom on the liver, the suspension of MGL-3196 (0.3, 1, 3, 10 mg/kg) was administered by gavage to DIO mice for 23 consecutive days.
RESULTS: Resmetirom demonstrated good exposure and reasonable oral bioavailability in rats. Both the distribution volume and the clearance rate are relatively low. For the MGL-3196 suspension orally administered to DIO mice, an increased exposure in the dose ratio was observed [1]. Among the animals treated with McL-3196, both cholesterol and liver size decreased, which was mainly due to the reduction of triglycerides in the liver. Among the animals treated with McL-3196, there was no effect on bone mineral density (BMD), heart or kidney size [1].
METHODS: To study the improvement of liver pathological characteristics by Resmetirom, mouse models of non-alcoholic steatohepatitis (NASH) were treated with Resmetirom(3 mg/kg, 5 mg/kg).
RESULTS: In the NASH mouse model, Resmetirom was able to significantly improve the pathological characteristics of the liver. Through the oil red O staining experiment, it was found that Resmetirom could effectively reduce liver fat accumulation, and the effect was more obvious in the high-dose group (5 mg/kg). In addition, Resmetirom can also improve liver fibrosis and inflammation caused by NASH by restoring the expression of RGS5 and inhibiting the activation of STAT3 and NF-κB signaling pathways. [2]