MGL-3196 | Resmetirom | CAS#920509-32-6 | thyroid hormone receptor-β agonist

MedKoo Cat#: 522371 | Name: Resmetirom

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Resmetirom

CAS#920509-32-6

Theoretical Analysis

MedKoo Cat#: 522371

Name: Resmetirom

CAS#: 920509-32-6

Chemical Formula: C17H12Cl2N6O4

Exact Mass: 434.0297

Molecular Weight: 435.22

Elemental Analysis: C, 46.92; H, 2.78; Cl, 16.29; N, 19.31; O, 14.70

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 6,450.00	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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T8Z11C23

View CoA: current batch, Lot#T7K09C06

QC Data

View QC data: current batch, Lot#T7K09C06

View QC data: current batch, Lot#T8Z11C23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	125.0	287.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Ratziu V, Scanlan TS, Bruinstroop E. Thyroid hormone receptor-β analogs for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH). J Hepatol. 2024 Oct 18:S0168-8278(24)02639-4. doi: 10.1016/j.jhep.2024.10.018. Epub ahead of print. PMID: 39428045. 2: Chen VL, Morgan TR, Rotman Y, Patton HM, Cusi K, Kanwal F, Kim WR. Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD Practice Guidance. Hepatology. 2024 Oct 18. doi: 10.1097/HEP.0000000000001112. Epub ahead of print. PMID: 39422487. 3: Sinha RA, Bruinstroop E, Yen PM. Actions of thyroid hormones and thyromimetics on the liver. Nat Rev Gastroenterol Hepatol. 2024 Oct 17. doi: 10.1038/s41575-024-00991-4. Epub ahead of print. PMID: 39420154. 4: Nielsen MH, Nøhr-Meldgaard J, Møllerhøj MB, Oró D, Pors SE, Andersen MW, Kamzolas I, Petsalaki E, Vacca M, Harder LM, Perfield JW, Veidal S, Hansen HH, Feigh M. Characterization of six clinical drugs and dietary intervention in the non-obese CDAA-HFD mouse model of MASH and progressive fibrosis. Am J Physiol Gastrointest Liver Physiol. 2024 Oct 15. doi: 10.1152/ajpgi.00110.2024. Epub ahead of print. PMID: 39404770. 5: Sinha RA. Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease. Endocrinol Metab (Seoul). 2024 Oct 14. doi: 10.3803/EnM.2024.2068. Epub ahead of print. PMID: 39397515. 6: Younossi ZM, Paik JM, Henry L, Stepanova M, Nader F. Pharmaco-Economic Assessment of Screening Strategies for High-Risk MASLD in Primary Care. Liver Int. 2024 Oct 7. doi: 10.1111/liv.16119. Epub ahead of print. PMID: 39373093. 7: Hashim HT, Alhatemi AQM, Riaz S, Al-Ghuraibawi MA, Alabide AS, Saeed H, Sulaiman FA, Alhussain MAA, Shallan MA, Al-Obaidi AD, Saab O, Al-Obaidi H, Hashim AT, Merza N. Unveiling Resmetirom: A systematic review and meta-analysis on its impact on liver function and safety in non-alcoholic steatohepatitis treatment. JGH Open. 2024 Oct 1;8(10):e70025. doi: 10.1002/jgh3.70025. PMID: 39359614; PMCID: PMC11444049. 8: Dixon ED, Claudel T, Nardo AD, Riva A, Fuchs C, Mlitz V, Busslinger G, Schnarnagl H, Stojakovic T, Senéca J, Hinteregger H, Grabner GF, Kratky D, Verkade H, Zimmermann R, Haemmerle G, Trauner M. Inhibition of ATGL alleviates MASH via impaired PPARα signalling that favours hydrophilic bile acid composition in mice. J Hepatol. 2024 Sep 30:S0168-8278(24)02577-7. doi: 10.1016/j.jhep.2024.09.037. Epub ahead of print. PMID: 39357546. 9: Shahi A, Yadav A, Rajak S, Raza S, Tewari A, Gupta P, Sinha RA. Liver- specific thyroid hormone receptor-β agonism alleviates alcoholic steatohepatitis (ASH) in mice. Biochem Biophys Res Commun. 2024 Nov 19;734:150742. doi: 10.1016/j.bbrc.2024.150742. Epub 2024 Sep 24. PMID: 39353359. 10: Xia M, Varmazyad M, Pla-Palacín I, Gavlock DC, DeBiasio R, LaRocca G, Reese C, Florentino RM, Faccioli LAP, Brown JA, Vernetti LA, Schurdak M, Stern AM, Gough A, Behari J, Soto-Gutierrez A, Taylor DL, Miedel MT. Comparison of wild- type and high-risk PNPLA3 variants in a human biomimetic liver microphysiology system for metabolic dysfunction-associated steatotic liver disease precision therapy. Front Cell Dev Biol. 2024 Sep 11;12:1423936. doi: 10.3389/fcell.2024.1423936. PMID: 39324073; PMCID: PMC11422722. 11: Ayesh H. Comparative Efficacy and Safety of Resmetirom Versus Semaglutide in Treating MASH and MASLD: A Network Meta-Analysis. Am J Ther. 2024 Sep 19. doi: 10.1097/MJT.0000000000001808. Epub ahead of print. PMID: 39297757. 12: Brisnovali NF, Haney C, Goedeke L. Rezdiffra™ (resmetirom): a THR-β agonist for non-alcoholic steatohepatitis. Trends Pharmacol Sci. 2024 Sep 19:S0165-6147(24)00184-6. doi: 10.1016/j.tips.2024.08.009. Epub ahead of print. PMID: 39304473. 13: Ezhilarasan D. Beyond resmetirom approval for NAFLD: what has to be done? Drug Discov Today. 2024 Sep 19;29(11):104185. doi: 10.1016/j.drudis.2024.104185. Epub ahead of print. PMID: 39304033. 14: Fishman J, Kim Y, Charlton MR, Smith ZJ, O'Connell T, Bercaw EM. Estimation of the Eligible Population For Resmetirom Among Adults in the United States for Treatment of Non-Cirrhotic NASH with Moderate-to-Advanced Liver Fibrosis. Adv Ther. 2024 Nov;41(11):4172-4190. doi: 10.1007/s12325-024-02989-5. Epub 2024 Sep 18. PMID: 39292422; PMCID: PMC11480167. 15: Ohri S, Summa M. Resmetirom (Rezdiffra) for the Treatment of Noncirrhotic Nonalcoholic Steatohepatitis With Moderate to Advanced Fibrosis. Am Fam Physician. 2024 Sep;110(3):313-314. PMID: 39283860. 16: Younossi ZM, Stepanova M, Racila A, Henry L, Labriola D, Taub R, Nader F. Health-related quality of life (HRQL) assessments in a 52-week, double-blind, randomized, placebo-controlled phase III study of resmetirom (MGL-3196) in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Hepatology. 2024 Sep 6. doi: 10.1097/HEP.0000000000001084. Epub ahead of print. PMID: 39250515. 17: Mazhar S, Azhar A, Khan A, Shakil G, Kumari S, Devi D, Jawad S. Efficacy and safety of resmetirom among patients with non-alcoholic steatohepatitis: a systematic review and meta-analysis. Ann Med Surg (Lond). 2024 Jul 15;86(9):5447-5454. doi: 10.1097/MS9.0000000000002314. PMID: 39239031; PMCID: PMC11374252. 18: Flavin B. Nonalcoholic steatohepatitis/metabolic dysfunction-associated steatohepatitis emerging market: Preparing managed care for early intervention, equitable access, and integrating the patient perspective. J Manag Care Spec Pharm. 2024 Sep;30(9-a Suppl):S1-S13. doi: 10.18553/jmcp.2024.30.9-a.s1. PMID: 39213163; PMCID: PMC11365455. 19: Zhou YH, Kehar M, Ng NBH, Zheng MH. Letter: Resmetirom for treatment of MASH with children and adolescents. Aliment Pharmacol Ther. 2024 Aug 30. doi: 10.1111/apt.18212. Epub ahead of print. PMID: 39214864. 20: Radosavljevic T, Brankovic M, Samardzic J, Djuretić J, Vukicevic D, Vucevic D, Jakovljevic V. Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches. Antioxidants (Basel). 2024 Jul 26;13(8):906. doi: 10.3390/antiox13080906. PMID: 39199152; PMCID: PMC11351122.