resmetirom   Click here for help

GtoPdb Ligand ID: 12026

Synonyms: compound 53 [PMID: 24712661] | MGL-3196 | MGL3196 | Rezdiffra® | VIA-3196 | VIA3196
Approved drug
resmetirom is an approved drug (FDA (2024))
Compound class: Synthetic organic
Comment: Resmetirom (MGL-3196) was developed as a thyroid receptor β (THRβ)-selective agonist, for potential to treat non-alcoholic steatohepatitis (NASH) and heterozygous familial hypercholesterolemia, with reduced potential to cause side-effects associated with THRα activation outside the liver [6].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 146
Molecular weight 434.03
XLogP 3.45
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES N#Cc1nn(c2cc(Cl)c(c(c2)Cl)Oc2n[nH]c(=O)c(c2)C(C)C)c(=O)[nH]c1=O
Isomeric SMILES Clc1cc(cc(c1Oc1n[nH]c(=O)c(c1)C(C)C)Cl)n1nc(c(=O)[nH]c1=O)C#N
InChI 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)
InChI Key FDBYIYFVSAHJLY-UHFFFAOYSA-N
References
1. Harrison SA, Bashir M, Moussa SE, McCarty K, Pablo Frias J, Taub R, Alkhouri N. (2021)
Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH.
Hepatol Commun, 5 (4): 573-588. [PMID:33860116]
2. Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, Alkhouri N, Bansal MB, Baum S, Neuschwander-Tetri BA et al.. (2019)
Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
Lancet, 394 (10213): 2012-2024. [PMID:31727409]
3. Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, Labriola D, Moussa SE, Neff GW, Rinella ME et al.. (2024)
A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis.
N Engl J Med, 390 (6): 497-509. [PMID:38324483]
4. Harrison SA, Ratziu V, Anstee QM, Noureddin M, Sanyal AJ, Schattenberg JM, Bedossa P, Bashir MR, Schneider D, Taub R et al.. (2024)
Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis.
Aliment Pharmacol Ther, 59 (1): 51-63. [PMID:37786277]
5. Harrison SA, Taub R, Neff GW, Lucas KJ, Labriola D, Moussa SE, Alkhouri N, Bashir MR. (2023)
Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial.
Nat Med, 29 (11): 2919-2928. [PMID:37845512]
6. Kelly MJ, Pietranico-Cole S, Larigan JD, Haynes NE, Reynolds CH, Scott N, Vermeulen J, Dvorozniak M, Conde-Knape K, Huang KS et al.. (2014)
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.
J Med Chem, 57 (10): 3912-23. [PMID:24712661]
7. Ray K. (2024)
Resmetirom proves positive for NASH with liver fibrosis.
Nat Rev Gastroenterol Hepatol, [Epub ahead of print]. [PMID:38360990]
8. Ray K. (2024)
Resmetirom safe for nonalcoholic fatty liver disease.
Nat Rev Gastroenterol Hepatol, 21 (1): 2. [PMID:37990099]
9. Younossi ZM, Stepanova M, Taub RA, Barbone JM, Harrison SA. (2022)
Hepatic Fat Reduction Due to Resmetirom in Patients With Nonalcoholic Steatohepatitis Is Associated With Improvement of Quality of Life.
Clin Gastroenterol Hepatol, 20 (6): 1354-1361.e7. [PMID:34329774]