Resmetirom
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MedKoo CAT#: 522371

CAS#: 920509-32-6

Description: Resmetirom, also known as MGL-3196, is a potent and highly selective thyroid hormone receptor β agonist in clinical trials for the treatment of dyslipidemia. The beneficial effects of thyroid hormone (TH) on lipid levels are primarily due to its action at the thyroid hormone receptor β (THR-β) in the liver, while adverse effects, including cardiac effects, are mediated by thyroid hormone receptor α (THR-α).

Chemical Structure

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Resmetirom
CAS# 920509-32-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522371
Name: Resmetirom
CAS#: 920509-32-6
Chemical Formula: C17H12Cl2N6O4
Exact Mass: 434.03
Molecular Weight: 435.220
Elemental Analysis: C, 46.92; H, 2.78; Cl, 16.29; N, 19.31; O, 14.70

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3650 Ready to ship
2g USD 6450 Ready to ship
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Synonym: MGL-3196; MGL 3196; MGL3196; VIA 3196; VIA3196; VIA-3196; Resmetirom.

IUPAC/Chemical Name: 2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile

InChi Key: FDBYIYFVSAHJLY-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: N#CC1=NN(C2=CC(Cl)=C(OC(C=C3C(C)C)=NNC3=O)C(Cl)=C2)C(NC1=O)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Resmetirom, or MGL-3196, shows outstanding safety in a rat heart model and is efficacious in a preclinical model at doses that showed no impact on the central thyroid axis.

Biological target: Resmetirom is a highly selective thyroid hormone receptor β (THR-β) agonist with an EC50 value of 0.21 μM.
In vitro activity: MGL-3196 had a high efficacy (90% that of T3) in activating TRβ, while the activation of TRα was only 25%. The results from this study indicate that MGL-3196's hepatic thyromimetic action results from a combination of hepatocyte-specific transport by OATP1B1 and the selective activation of TRβ over TRα. Reference: Int J Mol Sci. 2022 Nov 8;23(22):13714. https://pubmed.ncbi.nlm.nih.gov/36430194/
In vivo activity: Non-alcoholic steatohepatitis with fibrosis treatment with resmetirom did not influence mouse body weight. However, resmetirom treatment did lead to significant reduction in liver weight, hepatic steatosis, plasma alanine aminotransferase activity, liver and plasma cholesterol, and blood glucose. These metabolic effects translated into significant improvement in non-alcoholic fatty liver disease activity score. Reference: Br J Pharmacol. 2021 Jun;178(12):2412-2423. https://pubmed.ncbi.nlm.nih.gov/33655500/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 125.0 287.21

Preparing Stock Solutions

The following data is based on the product molecular weight 435.22 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Hönes GS, Sivakumar RG, Hoppe C, König J, Führer D, Moeller LC. Cell-Specific Transport and Thyroid Hormone Receptor Isoform Selectivity Account for Hepatocyte-Targeted Thyromimetic Action of MGL-3196. Int J Mol Sci. 2022 Nov 8;23(22):13714. doi: 10.3390/ijms232213714. PMID: 36430194; PMCID: PMC9691000. 2. Kannt A, Wohlfart P, Madsen AN, Veidal SS, Feigh M, Schmoll D. Activation of thyroid hormone receptor-β improved disease activity and metabolism independent of body weight in a mouse model of non-alcoholic steatohepatitis and fibrosis. Br J Pharmacol. 2021 Jun;178(12):2412-2423. doi: 10.1111/bph.15427. Epub 2021 Apr 6. PMID: 33655500. 3. Wang X, Wang L, Geng L, Tanaka N, Ye B. Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner. Int J Mol Sci. 2023 Mar 19;24(6):5843. doi: 10.3390/ijms24065843. PMID: 36982915; PMCID: PMC10058113.
In vitro protocol: 1. Hönes GS, Sivakumar RG, Hoppe C, König J, Führer D, Moeller LC. Cell-Specific Transport and Thyroid Hormone Receptor Isoform Selectivity Account for Hepatocyte-Targeted Thyromimetic Action of MGL-3196. Int J Mol Sci. 2022 Nov 8;23(22):13714. doi: 10.3390/ijms232213714. PMID: 36430194; PMCID: PMC9691000.
In vivo protocol: 1. Kannt A, Wohlfart P, Madsen AN, Veidal SS, Feigh M, Schmoll D. Activation of thyroid hormone receptor-β improved disease activity and metabolism independent of body weight in a mouse model of non-alcoholic steatohepatitis and fibrosis. Br J Pharmacol. 2021 Jun;178(12):2412-2423. doi: 10.1111/bph.15427. Epub 2021 Apr 6. PMID: 33655500. 2. Wang X, Wang L, Geng L, Tanaka N, Ye B. Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner. Int J Mol Sci. 2023 Mar 19;24(6):5843. doi: 10.3390/ijms24065843. PMID: 36982915; PMCID: PMC10058113.

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1: Hönes GS, Sivakumar RG, Hoppe C, König J, Führer D, Moeller LC. Cell-Specific Transport and Thyroid Hormone Receptor Isoform Selectivity Account for Hepatocyte-Targeted Thyromimetic Action of MGL-3196. Int J Mol Sci. 2022 Nov 8;23(22):13714. doi: 10.3390/ijms232213714. PMID: 36430194; PMCID: PMC9691000.


2: Hatziagelaki E, Paschou SA, Schön M, Psaltopoulou T, Roden M. NAFLD and thyroid function: pathophysiological and therapeutic considerations. Trends Endocrinol Metab. 2022 Nov;33(11):755-768. doi: 10.1016/j.tem.2022.08.001. Epub 2022 Sep 26. PMID: 36171155.


3: Javanbakht M, Fishman J, Moloney E, Rydqvist P, Ansaripour A. Early Cost- Effectiveness and Price Threshold Analyses of Resmetirom: An Investigational Treatment for Management of Nonalcoholic Steatohepatitis. Pharmacoecon Open. 2022 Sep 14. doi: 10.1007/s41669-022-00370-2. Epub ahead of print. PMID: 36104546.


4: Wirth EK, Puengel T, Spranger J, Tacke F. Thyroid hormones as a disease modifier and therapeutic target in nonalcoholic steatohepatitis. Expert Rev Endocrinol Metab. 2022 Sep;17(5):425-434. doi: 10.1080/17446651.2022.2110864. Epub 2022 Aug 11. PMID: 35957531.


5: Kovalic AJ. Pharmacotherapeutic Impact on Nonalcoholic Steatohepatitis Histology: A Systematic Review and Network Meta-analysis. J Clin Exp Hepatol. 2022 Jul-Aug;12(4):1057-1068. doi: 10.1016/j.jceh.2022.01.011. Epub 2022 Feb 1. PMID: 35814516; PMCID: PMC9257887.


6: Vijayakumar A, Okesli-Armlovich A, Wang T, Olson I, Seung M, Kusam S, Hollenback D, Mahadevan S, Marchand B, Toteva M, Breckenridge DG, Trevaskis JL, Bates J. Combinations of an acetyl CoA carboxylase inhibitor with hepatic lipid modulating agents do not augment antifibrotic efficacy in preclinical models of NASH and fibrosis. Hepatol Commun. 2022 Sep;6(9):2298-2309. doi: 10.1002/hep4.2011. Epub 2022 Jun 23. PMID: 35735253; PMCID: PMC9426400.


7: Chew NWS, Ng CH, Muthiah MD, Sanyal AJ. Comprehensive Review and Updates on Holistic Approach Towards Non-Alcoholic Fatty Liver Disease Management with Cardiovascular Disease. Curr Atheroscler Rep. 2022 Jul;24(7):515-532. doi: 10.1007/s11883-022-01027-5. Epub 2022 May 4. PMID: 35507280.


8: Hovingh GK, Klausen IC, Heggen E, McCarty K, Zhou R, Isaac BF, Taub R, Langslet G, Kastelein JJP. Resmetirom (MGL-3196) in Patients With Heterozygous Familial Hypercholesterolemia. J Am Coll Cardiol. 2022 Mar 29;79(12):1220-1222. doi: 10.1016/j.jacc.2022.01.023. PMID: 35331419.


9: Aggarwal P, Noureddin M, Harrison S, Jeannin S, Alkhouri N. Nonalcoholic steatohepatitis (NASH) cirrhosis: a snapshot of therapeutic agents in clinical development and the optimal design for clinical trials. Expert Opin Investig Drugs. 2022 Feb;31(2):163-172. doi: 10.1080/13543784.2022.2032640. Epub 2022 Feb 10. PMID: 35060815.


10: Caddeo A, Kowalik MA, Serra M, Runfola M, Bacci A, Rapposelli S, Columbano A, Perra A. TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD. Int J Mol Sci. 2021 Dec 3;22(23):13105. doi: 10.3390/ijms222313105. PMID: 34884910; PMCID: PMC8657920.


11: Fraile JM, Palliyil S, Barelle C, Porter AJ, Kovaleva M. Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease. Drug Des Devel Ther. 2021 Sep 22;15:3997-4009. doi: 10.2147/DDDT.S315724. PMID: 34588764; PMCID: PMC8473845.


12: Younossi ZM, Stepanova M, Taub RA, Barbone JM, Harrison SA. Hepatic Fat Reduction Due to Resmetirom in Patients With Nonalcoholic Steatohepatitis Is Associated With Improvement of Quality of Life. Clin Gastroenterol Hepatol. 2022 Jun;20(6):1354-1361.e7. doi: 10.1016/j.cgh.2021.07.039. Epub 2021 Jul 27. PMID: 34329774.


13: Fröhlich E, Wahl R. Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients. Front Endocrinol (Lausanne). 2021 Apr 26;12:587518. doi: 10.3389/fendo.2021.587518. PMID: 33981284; PMCID: PMC8109250.


14: Harrison SA, Bashir M, Moussa SE, McCarty K, Pablo Frias J, Taub R, Alkhouri N. Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH. Hepatol Commun. 2021 Jan 4;5(4):573-588. doi: 10.1002/hep4.1657. PMID: 33860116; PMCID: PMC8034581.


15: Kannt A, Wohlfart P, Madsen AN, Veidal SS, Feigh M, Schmoll D. Activation of thyroid hormone receptor-β improved disease activity and metabolism independent of body weight in a mouse model of non-alcoholic steatohepatitis and fibrosis. Br J Pharmacol. 2021 Jun;178(12):2412-2423. doi: 10.1111/bph.15427. Epub 2021 Apr 6. PMID: 33655500.


16: Patikorn C, Veettil SK, Phisalprapa P, Pham T, Kowdley KV, Chaiyakunapruk N. Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis. Ann Hepatol. 2021 Sep-Oct;24:100315. doi: 10.1016/j.aohep.2021.100315. Epub 2021 Jan 27. PMID: 33515800.


17: Shen B, Lu LG. Efficacy and safety of drugs for nonalcoholic steatohepatitis. J Dig Dis. 2021 Feb;22(2):72-82. doi: 10.1111/1751-2980.12967. PMID: 33385317.


18: Luong XG, Stevens SK, Jekle A, Lin TI, Gupta K, Misner D, Chanda S, Mukherjee S, Williams C, Stoycheva A, Blatt LM, Beigelman LN, Symons JA, Raboisson P, McGowan D, Vandyck K, Deval J. Regulation of gene transcription by thyroid hormone receptor β agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH). PLoS One. 2020 Dec 11;15(12):e0240338. doi: 10.1371/journal.pone.0240338. PMID: 33306682; PMCID: PMC7732128.


19: Guirguis E, Grace Y, Bolson A, DellaVecchia MJ, Ruble M. Emerging therapies for the treatment of nonalcoholic steatohepatitis: A systematic review. Pharmacotherapy. 2021 Mar;41(3):315-328. doi: 10.1002/phar.2489. Epub 2021 Feb 17. PMID: 33278029.


20: Jeong SW. Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming. Diabetes Metab J. 2020 Oct;44(5):640-657. doi: 10.4093/dmj.2020.0115. Epub 2020 Oct 21. PMID: 33115209; PMCID: PMC7643594.