Resmetirom is a synthetic, orally active thyroid hormone receptor-beta (THR-β) partial agonist developed to target thyroid hormone signaling in the liver. It is the active pharmaceutical ingredient in REZDIFFRA and is used with diet and exercise for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH, with moderate to advanced liver fibrosis consistent with stages F2–F3. The current FDA label states that this indication was approved under accelerated approval.
Resmetirom is identified by CAS No. 920509-32-6, molecular formula C17H12Cl2N6O4, and molecular weight 435.22 g/mol. PubChem identifies the substance as MGL-3196 and provides the same CAS number and molecular formula.
Resmetirom is a small-molecule chemical entity containing dichlorophenyl, pyridazinone, triazinedione and nitrile structural functionalities. Its systematic chemical name is:
2-[3,5-Dichloro-4-((6-oxo-5-(propan-2-yl)-1,6-dihydropyridazin-3-yl)oxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile.
The FDA label confirms the molecular formula C17H12Cl2N6O4 and molecular weight 435.22 g/mol. PubChem reports an exact mass of 434.0297083 Da, XLogP3-AA of 2.7, hydrogen-bond donor count of 2, hydrogen-bond acceptor count of 7, 4 rotatable bonds, and topological polar surface area of 136 Ų.
Resmetirom is used in conjunction with diet and exercise for adults with noncirrhotic MASH with moderate to advanced liver fibrosis (F2–F3). The current FDA indication uses the term MASH, replacing the formerly used term NASH.
The drug is supplied as oral tablets in 60 mg, 80 mg and 100 mg strengths.
Resmetirom is designed to act preferentially through hepatic THR-β signaling, an important pathway involved in liver lipid metabolism. FDA clinical pharmacology information reports reductions in liver fat measured by MRI-PDFF and controlled attenuation parameter, as well as reductions in certain noninvasive liver disease markers.
Resmetirom is a partial agonist of thyroid hormone receptor-beta (THR-β). THR-β is the predominant thyroid hormone receptor subtype in the liver. Activation of hepatic THR-β promotes pathways involved in lipid metabolism and reduces intrahepatic triglyceride content.
In an FDA-described in-vitro functional assay, resmetirom produced 83.8% of the maximum response relative to triiodothyronine (T3) at THR-β, with an EC50 of 0.21 μM. At THR-α, it produced 48.6% efficacy relative to T3 with an EC50 of 3.74 μM, supporting its receptor-selective pharmacological profile.
Resmetirom is also highly protein-bound, with FDA clinical pharmacology documentation reporting approximately 99% protein binding and a plasma half-life of approximately 4.5 hours.
Quality control for Resmetirom API may include:
A universal current numerical API release specification for assay and individual impurities was not identified in the authoritative public sources reviewed. Therefore, unsupported numerical acceptance limits should not be presented as universal specifications.
Resmetirom is a synthetic small-molecule API requiring controlled chemical synthesis, purification and crystallization/solid-state control as applicable. Pharmaceutical manufacturing should incorporate validated process controls and analytical methods capable of monitoring the active substance and process-related/degradation impurities.
Because the molecule is intended for a highly regulated pharmaceutical product, manufacturing controls should address identity, assay, impurity profile, residual solvents, elemental impurities, physical properties and stability.
| Property | Verified Value |
|---|---|
| Appearance | Product-specific; verified release description should follow applicable specification |
| Molecular Formula | C17H12Cl2N6O4 |
| Molecular Weight | 435.22 g/mol |
| CAS Number | 920509-32-6 |
| PubChem CID | 15981237 |
| Exact Mass | 434.0297083 Da |
| XLogP3-AA | 2.7 |
| H-Bond Donors | 2 |
| H-Bond Acceptors | 7 |
| Rotatable Bonds | 4 |
| Topological Polar Surface Area | 136 Ų |
| Aqueous Solubility | 0.44 mg/mL at pH 7.04 |
| Solubility Profile | Low below pH 6; higher above pH 7 |
The FDA label specifically reports low aqueous solubility below pH 6 and 0.44 mg/mL at pH 7.04.
For the approved finished product, REZDIFFRA tablets are stored at 20–25°C (68–77°F), with excursions permitted to 15–30°C (59–86°F).
For bulk Resmetirom API, packaging should provide appropriate protection against moisture, contamination and environmental exposure. The exact container-closure system and storage conditions should be based on validated API stability data and the applicable product specification.
Typical documentation for Resmetirom API may include:
A qualified Resmetirom API manufacturer in India should maintain robust controls for chemical synthesis, purification, impurity management and solid-state quality.
For Resmetirom, analytical control of related substances and degradation products is particularly important because the API is used in a recently approved treatment for metabolic liver disease. A manufacturer should therefore maintain validated analytical procedures, controlled manufacturing processes, appropriate packaging and complete batch documentation.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.50% |
| Water Content | NMT 1.0% |