Resmetirom

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 Search

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

Molecular Formula	C17H12Cl2N6O4
Molecular Weight	435.221
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.madrigalpharma.com/ourapproach/mgl3196/ | https://www.ncbi.nlm.nih.gov/pubmed/24712661

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thyroid hormone receptor beta-1 26 Target ID: CHEMBL1947 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24712661 \| http://www.madrigalpharma.com/ourapproach/mgl3196/	Agonist 2752		0.21 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nonalcoholic steatohepatitis 9 Sources: https://clinicaltrials.gov/ct2/show/NCT02912260 http://adisinsight.springer.com/drugs/800029404	Primary		Phase II 1147	Unknown Approved Use Unknown
Heterozygous familial hypercholesterolemia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT03038022 http://adisinsight.springer.com/drugs/800029404	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1.71 μg/mL EXPERIMENT https://pubs.acs.org/doi/10.1021/jm4019299	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

Value	Dose	Co-administered	Analyte	Population
17.4 μg × h/mL EXPERIMENT https://pubs.acs.org/doi/10.1021/jm4019299	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.08 h EXPERIMENT https://pubs.acs.org/doi/10.1021/jm4019299	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/24075770	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/24075770	Sources: https://pubmed.ncbi.nlm.nih.gov/24075770

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 2438		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A4/5 296 CYP2C19 2057

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24712661/	unlikely [IC50 >50 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24712661/	unlikely [IC50 >50 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24712661/	weak [IC50 >= 22 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/24712661/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01DPBQ	https://www.1pchem.com/search?query=1P01DPBQ
AK Scientific	2544AH	https://aksci.com/item_detail.php?cat=2544AH
AstaTech	C77150	http://astatechinc.com/CPSResult.php?CRNO=C77150
Axon MedChem	2657	https://www.axonmedchem.com/product/2657
Chem Scene	CS-6179	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6179
ChemShuttle	186231	https://www.chemshuttle.com/catalogsearch/result/?q=186231
eMolecules	49383305	https://orderbb.emolecules.com/search/#?query=49383305
Excenen	EX-A2477	http://www.excenen.com/searchresultlist.php?id=EX-A2477
mcule	MCULE-7627092136	https://mcule.com/MCULE-7627092136/
MedChem Express	HY-12216	https://www.medchemexpress.com/search.html?q=HY-12216&ft=&fa=&fp=
Molnova	M16604	https://www.molnova.com/en/serch-list.html?keywords=M16604
MolPort	MolPort-035-395-778	https://www.molport.com/shop/molecule-link/MolPort-035-395-778
MuseChem	I007979	https://www.musechem.com/product/I007979.html
ShangHai Biochempartner	BCP24624	http://www.biochempartner.com/search_BCP24624

PubMed

Title	Date	PubMed
Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist.	2013 Oct	24075770
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	24712661

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:10:28 GMT 2025` Edited by `admin` on `Mon Mar 31 22:10:28 GMT 2025`
Record UNII	RE0V0T1ES0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Resmetirom

Official Name

English

MGL-3196

Preferred Name

English

resmetirom [INN]

Common Name

English

REZDIFFRA

Brand 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

Resmetirom [WHO-DD]

Common Name

English

VIA-3196

Code

English

RESMETIROM [USAN]

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID601352610