Resmetirom

Storage temp: Inert atmosphere, Store in freezer, under -20°C

Solubility: DMSO: 59.0(Max Conc. mg/mL); 135.56(Max Conc. mM)

Form:  A Crystalline Solid

Color:  Yellow to Orange

1. Cell Experiment​​

​​DMSO:​​ 75 mg/mL (172.33 mM; Ultrasonic required)

Preparing Stock Solutions：

​​

Please prepare the stock solution in the appropriate solvent based on the product's solubility in different solvents. Once dissolved, aliquot the solution to avoid product inactivation caused by repeated freeze-thaw cycles.

​​Storage method and shelf life of the stock solution:​​ -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use within 2 years; when stored at -20°C, please use within 1 year.

​​2. Animal Experiment​​

Please select the appropriate dissolution protocol based on your experimental animals and administration method. For the following protocols, first prepare a clear stock solution in vitro, then add co-solvents in sequence:

To ensure reliable experimental results, the clear stock solution can be stored appropriately according to the storage conditions. For in vivo experiments, it is recommended to prepare the working solution fresh and use it on the same day.

The percentages shown before the solvents refer to the volume percentage of each solvent in the final solution. If precipitation occurs during preparation, heating and/or sonication can be used to aid dissolution.

​​Protocol 1​​

Add each solvent in the following order: 10% DMSO, 40% PEG300, 5% Tween-80, 45% Saline

​​Solubility:​​ ≥ 3.75 mg/mL (8.62 mM); Clear solution

This protocol yields a clear solution with a concentration of ≥ 3.75 mg/mL (8.62 mM, saturation unknown).

​​Preparation example for a 1 mL working solution:​​

Take 100 μL of the 37.5 mg/mL clear DMSO stock solution and add it to 400 μL of PEG300, mix well. Then add 50 μL of Tween-80 to the mixture and mix thoroughly. Finally, add 450 μL of normal saline to bring the volume to 1 mL.

​​Protocol 2​​

Add each solvent in the following order: 10% DMSO, 90% (20% SBE-β-CD in Saline)

​​Solubility:​​ ≥ 3.75 mg/mL (8.62 mM); Clear solution

This protocol yields a clear solution with a concentration of ≥ 3.75 mg/mL (8.62 mM, saturation unknown).

​​Preparation example for a 1 mL working solution:​​

Take 100 μL of the 37.5 mg/mL clear DMSO stock solution and add it to 900 μL of a 20% SBE-β-CD solution in saline, mix well.

​​Protocol 3​​

Add each solvent in the following order: 10% DMSO, 90% Corn Oil

​​Solubility:​​ ≥ 3.75 mg/mL (8.62 mM); Clear solution

This protocol yields a clear solution with a concentration of ≥ 3.75 mg/mL (8.62 mM, saturation unknown). ​​This protocol is not suitable for experiments lasting longer than half a month.​​

​​Preparation example for a 1 mL working solution:​​

Take 100 μL of the 37.5 mg/mL clear DMSO stock solution and add it to 900 μL of corn oil, mix well.

Resmetirom is a partial agonist of the thyroid hormone receptor-beta (THR-β). Resmetirom produced 83.8% of the maximum response compared to triiodothyronine (T3), with an EC50 of 0.21 µM in an in vitro functional assay for THR-β activation. The same functional assay for thyroid hormone receptor-alpha (THR-α) agonism showed 48.6% efficacy for resmetirom relative to T3, with an EC50 of 3.74 µM.

Resmetirom decreases liver fat content and the concentrations of free thyroxine (FT4), which is a prohormone. Although it is inconclusive, there have been some reports in the literature suggesting that resmetirom may convert thyroxine (T4) to triiodothyronine (T3).3 It increases the concentrations of sex hormone-binding globulin.

Thyroid hormones, such as FT4 and free triiodothyronine (FT3), are key regulators of lipid metabolism in the liver. Thyroid hormone receptor-beta (THR-β) is the major form of the thyroid hormone receptor in the liver, and stimulation of this receptor reduces intrahepatic triglycerides. Many patients with non-alcoholic fatty liver disease (NAFLD) present with impaired thyroid function, such as hypothyroidism, rendering it a significant risk factor for NAFLD. Hypothyroidism has also been linked to dysregulated adipose tissue lipolysis and increased free fatty acid release from the adipose to the liver, promoting hepatic insulin resistance. Increased circulating levels of proinflammatory adipokines, which contribute to hepatic inflammation and fibrosis, may also be observed. Resmetirom is a partial agonist of THR-β that promotes lipophagy and hepatic fatty acid β-oxidation, thereby reducing liver fat. It is approximately 28 times more selective than FT3 for THR-β versus thyroid hormone receptor-alpha (THR-α), which is mainly expressed in the heart and bones.