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Details

Stereochemistry ACHIRAL
Molecular Formula C17H12Cl2N6O4
Molecular Weight 435.221
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Resmetirom

SMILES

CC(C)C1=CC(OC2=C(Cl)C=C(C=C2Cl)N3N=C(C#N)C(=O)NC3=O)=NNC1=O

InChI

InChIKey=FDBYIYFVSAHJLY-UHFFFAOYSA-N
InChI=1S/C17H12Cl2N6O4/c1-7(2)9-5-13(22-23-15(9)26)29-14-10(18)3-8(4-11(14)19)25-17(28)21-16(27)12(6-20)24-25/h3-5,7H,1-2H3,(H,23,26)(H,21,27,28)

HIDE SMILES / InChI
MGL-3196 is a first-in-class, orally administered, small-molecule, liver-directed, THR β-selective agonist. Preclinical, toxicology and Phase 1 clinical data suggest MGL-3196 has an attractive, differentiated profile as a potential treatment for non-alcoholic steatohepatitis (NASH) and dyslipidemias. THR-β selectivity also enhances the safety profile of MGL-3196, compared to non-selective agents. MGL-3196 has shown no suppression of the central thyroid axis, no THR-α effects on heart rate or bone, and no elevation of liver enzymes. These characteristics make MGL-3196 among the most promising molecules in development in this therapeutic area. MGL-3196 is in a Phase 2 clinical trial for the treatment of non-alcoholic steatohepatitis (NASH).

CNS Activity

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.71 μg/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
MGL-3196 plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
17.4 μg × h/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
MGL-3196 plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.08 h
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
MGL-3196 plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: p.375
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 6
Sources: Page: p.375
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
unlikely [IC50 >50 uM]
unlikely [IC50 >50 uM]
weak [IC50 ~22 uM]
Drug as victim

Drug as victim

Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist.
2013 Oct
Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a Highly Selective Thyroid Hormone Receptor β agonist in clinical trials for the treatment of dyslipidemia.
2014 May 22
Patents

Sample Use Guides

A two-week multiple dose study was conducted at doses of 5, 20, 50, 80, 100, and 200 mg per day in healthy subjects with mildly elevated low density lipoprotein (LDL) cholesterol. MGL-3196 was well-tolerated at all doses with no dose-related adverse events or liver enzyme, ECG or vital-sign changes. Doses ranging from 50 to 200 mg demonstrated highly statistically significant reductions relative to placebo of up to: 30% for LDL cholesterol (range, p = 0.05-<0.0001); 28% for non- high density lipoprotein (HDL) cholesterol (range, p = 0.027-0.0001); 24% for Apolipoprotein B (range, p = 0.008-0.0004), and statistical trends of up to 60% reduction in triglycerides (TG) (range, p = 0.13-0.016).
Route of Administration: Oral
MGL-3196 is 28-fold selective for THR-β (EC50=0.21 uM) over THR-α (EC50=3.74 uM ) in a functional assay. MGL-3196 shows an IC20 of roughly 30 uM for blockage of the hERG channel. The IC50 for CYP3A4/5 and for CYP2C19 is >50 uM, and there is only weak inhibition (roughly 22 uM) of CYP2C9.
Name Type Language
Resmetirom
INN  
Official Name English
resmetirom [INN]
Common Name English
1,2,4-Triazine-6-carbonitrile, 2-[3,5-dichloro-4-[[1,6-dihydro-5-(1-methylethyl)-6-oxo-3-pyridazinyl]oxy]phenyl]-2,3,4,5-tetrahydro-3,5-dioxo-
Systematic Name English
2-[3,5-Dichloro-4-[[1,6-dihydro-5-(1-methylethyl)-6-oxo-3-pyridazinyl]oxy]phenyl]-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carbonitrile
Systematic Name English
MGL-3196
Code English
VIA-3196
Code English
RESMETIROM [USAN]
Common Name English
Code System Code Type Description
USAN
GH-48
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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ChEMBL
CHEMBL3261331
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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PUBCHEM
15981237
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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SMS_ID
100000183599
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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INN
10850
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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DRUG BANK
DB12914
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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CAS
920509-32-6
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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FDA UNII
RE0V0T1ES0
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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NCI_THESAURUS
C170368
Created by admin on Sat Dec 16 08:33:56 GMT 2023 , Edited by admin on Sat Dec 16 08:33:56 GMT 2023
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