Sobetirome | CAS#211110-63-3 | thyroid hormone beta-receptor agonist

MedKoo Cat#: 319857 | Name: Sobetirome

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Description:

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

Sobetirome, also known as GC-1 and QRX-431, is a thyroid hormone receptor β (TRβ) agonist. Sobetirome inhibits proliferation but induces differentiation and TRβ mRNA expression in mouse and rat osteoblast-like cells. Sobetirome selectively binds to and activates TRβ over TRα and this receptor selectivity led to the hypothesis that sobetirome would lower cholesterol through activation of liver TRβ without stimulating cardiac function through TRα activation in the heart. The tissue selective thyromimetic properties of sobetirome have been demonstrated in numerous animal models, which led to its clinical development as a novel cholesterol-lowering agent.

Chemical Structure

Sobetirome

CAS#211110-63-3

Theoretical Analysis

MedKoo Cat#: 319857

Name: Sobetirome

CAS#: 211110-63-3

Chemical Formula: C20H24O4

Exact Mass: 328.1675

Molecular Weight: 328.41

Elemental Analysis: C, 73.15; H, 7.37; O, 19.49

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 400.00	2 weeks
25mg	USD 900.00	2 weeks

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Synonym

GC-1; GC1; GC 1; QRX-431; QRX 431; QRX431; Sobetirome

IUPAC/Chemical Name

2-(4-(4-hydroxy-3-isopropylbenzyl)-3,5-dimethylphenoxy)acetic acid

InChi Key

QNAZTOHXCZPOSA-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H24O4/c1-12(2)17-9-15(5-6-19(17)21)10-18-13(3)7-16(8-14(18)4)24-11-20(22)23/h5-9,12,21H,10-11H2,1-4H3,(H,22,23)

SMILES Code

O=C(O)COC1=CC(C)=C(CC2=CC=C(O)C(C(C)C)=C2)C(C)=C1

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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

Sobetirome is a thyroid hormone receptor β (TRβ)-specific agonist which bind selectively to TRβ-1 with an EC50 of 0.16 μM.

In vitro activity:

Sobetirome may be a promising thyromimetic compound targeting an important neuropathological hallmark of multiple system atrophy (MSA), a rare and rapidly progressive atypical Parkinsonian disorder. Sobetirome enhanced the production of myelin-related proteins in both normal and MSA-related cells. It also increased myelin length and quantity in oligodendrocytes. Reference: Eur J Neurosci. 2024 Jan;59(2):308-315. https://pubmed.ncbi.nlm.nih.gov/38086536/

In vivo activity:

Specific activation of TRβ by sobetirome impeded tumor growth and restored gene expression in colorectal cancer (CRC) tumors in mice. Tumor growth analysis showed that sobetirome profoundly inhibited tumor growth and 18FDG uptake. TRβ expression was decreased in CRC tumors; however, it was upregulated by sobetirome administration. Reference: J Recept Signal Transduct Res. 2022 Oct;42(5):495-502. https://pubmed.ncbi.nlm.nih.gov/35473566/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	100.0	304.51

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 328.41 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. Mészáros L, Himmler M, Schneider Y, Arnold P, Dörje F, Schubert DW, Winkler J. Sobetirome rescues α-synuclein-mediated demyelination in an in vitro model of multiple system atrophy. Eur J Neurosci. 2024 Jan;59(2):308-315. doi: 10.1111/ejn.16215. Epub 2023 Dec 12. PMID: 38086536. 2. Gu HJ, Ahn JS, Ahn GJ, Shin SH, Ryu BY. Restoration of PM2.5-induced spermatogonia GC-1 cellular damage by parthenolide via suppression of autophagy and inflammation: An in vitro study. Toxicology. 2023 Nov;499:153651. doi: 10.1016/j.tox.2023.153651. Epub 2023 Oct 17. PMID: 37858773. 3. Bohlen JF, Cleary CM, Das D, Sripathy SR, Sadowski N, Shim G, Kenney RF, Buchler IP, Banerji T, Scanlan TS, Mulkey DK, Maher BJ. Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt-Hopkins syndrome. Brain. 2023 Aug 1;146(8):3331-3346. doi: 10.1093/brain/awad057. PMID: 37068912; PMCID: PMC10393406. 4. Pourvali K, Shimi G, Ghorbani A, Shakery A, Shirazi FH, Zand H. Selective thyroid hormone receptor beta agonist, GC-1, is capable to reduce growth of colorectal tumor in syngeneic mouse models. J Recept Signal Transduct Res. 2022 Oct;42(5):495-502. doi: 10.1080/10799893.2022.2032748. Epub 2022 Apr 27. PMID: 35473566.

In vitro protocol:

In vivo protocol:

1. Bohlen JF, Cleary CM, Das D, Sripathy SR, Sadowski N, Shim G, Kenney RF, Buchler IP, Banerji T, Scanlan TS, Mulkey DK, Maher BJ. Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt-Hopkins syndrome. Brain. 2023 Aug 1;146(8):3331-3346. doi: 10.1093/brain/awad057. PMID: 37068912; PMCID: PMC10393406. 2. Pourvali K, Shimi G, Ghorbani A, Shakery A, Shirazi FH, Zand H. Selective thyroid hormone receptor beta agonist, GC-1, is capable to reduce growth of colorectal tumor in syngeneic mouse models. J Recept Signal Transduct Res. 2022 Oct;42(5):495-502. doi: 10.1080/10799893.2022.2032748. Epub 2022 Apr 27. PMID: 35473566.

1: Pesce E, Benitez-Gonzalez J, Tindall AJ, Lemkine GF, Robin-Duchesne B, Sachs LM, Pasquier EDD. Testing the sensitivity of the medaka Transgenic Eleuthero- embryonic THYroid-Specific assay (TETHYS) to different mechanisms of action. Aquat Toxicol. 2024 Sep 10;276:107081. doi: 10.1016/j.aquatox.2024.107081. Epub ahead of print. PMID: 39305711. 2: Hochbaum DR, Hulshof L, Urke A, Wang W, Dubinsky AC, Farnsworth HC, Hakim R, Lin S, Kleinberg G, Robertson K, Park C, Solberg A, Yang Y, Baynard C, Nadaf NM, Beron CC, Girasole AE, Chantranupong L, Cortopassi MD, Prouty S, Geistlinger L, Banks AS, Scanlan TS, Datta SR, Greenberg ME, Boulting GL, Macosko EZ, Sabatini BL. Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration. Cell. 2024 Aug 19:S0092-8674(24)00835-3. doi: 10.1016/j.cell.2024.07.041. Epub ahead of print. PMID: 39178853. 3: Mészáros L, Himmler M, Schneider Y, Arnold P, Dörje F, Schubert DW, Winkler J. Sobetirome rescues α-synuclein-mediated demyelination in an in vitro model of multiple system atrophy. Eur J Neurosci. 2024 Jan;59(2):308-315. doi: 10.1111/ejn.16215. Epub 2023 Dec 12. PMID: 38086536. 4: Gillis NE, Cozzens LM, Wilson ER, Smith NM, Tomczak JA, Bolf EL, Carr FE. TRβ Agonism Induces Tumor Suppression and Enhances Drug Efficacy in Anaplastic Thyroid Cancer in Female Mice. Endocrinology. 2023 Aug 28;164(10):bqad135. doi: 10.1210/endocr/bqad135. PMID: 37702560; PMCID: PMC10506733. 5: Xu ST, Jin HW, Jin X, Xu BX, Zhang Y, Xie T, Wang G, Wang J, Zhen L. Development and validation for bioanalysis of VK2809, its active metabolite VK2809A and glutathione-conjugated metabolite MB06588 in rat liver using LC- MS/MS. J Pharm Biomed Anal. 2023 Sep 20;234:115595. doi: 10.1016/j.jpba.2023.115595. Epub 2023 Jul 21. PMID: 37487290. 6: Bohlen JF, Cleary CM, Das D, Sripathy SR, Sadowski N, Shim G, Kenney RF, Buchler IP, Banerji T, Scanlan TS, Mulkey DK, Maher BJ. Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt- Hopkins syndrome. Brain. 2023 Aug 1;146(8):3331-3346. doi: 10.1093/brain/awad057. PMID: 37068912; PMCID: PMC10393406. 7: Valcárcel-Hernández V, Guillén-Yunta M, Scanlan TS, Bárez-López S, Guadaño- Ferraz A. Maternal Administration of the CNS-Selective Sobetirome Prodrug Sob- AM2 Exerts Thyromimetic Effects in Murine MCT8-Deficient Fetuses. Thyroid. 2023 May;33(5):632-640. doi: 10.1089/thy.2022.0612. Epub 2023 Mar 17. PMID: 36792926; PMCID: PMC10171952. 8: Fan L, Kishore A, Jansen-Olliges L, Wang D, Stahl F, Psathaki OE, Harre J, Warnecke A, Weder J, Preller M, Zeilinger C. Identification of a Thyroid Hormone Binding Site in Hsp90 with Implications for Its Interaction with Thyroid Hormone Receptor Beta. ACS Omega. 2022 Aug 9;7(33):28932-28945. doi: 10.1021/acsomega.2c02331. PMID: 36033668; PMCID: PMC9404468. 9: Kim B, Ko YH, Runfola M, Rapposelli S, Ortore G, Chiellini G, Kim JH. Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis. Int J Mol Sci. 2021 Mar 28;22(7):3488. doi: 10.3390/ijms22073488. PMID: 33800546; PMCID: PMC8038088. 10: Ferrara SJ, Chaudhary P, DeBell MJ, Marracci G, Miller H, Calkins E, Pocius E, Napier BA, Emery B, Bourdette D, Scanlan TS. TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor. bioRxiv [Preprint]. 2021 Jan 27:2021.01.25.428149. doi: 10.1101/2021.01.25.428149. Update in: Cell Chem Biol. 2022 Feb 17;29(2):239-248.e4. doi: 10.1016/j.chembiol.2021.07.014. PMID: 33532772; PMCID: PMC7852265. 11: Chaudhary P, Marracci GH, Calkins E, Pocius E, Bensen AL, Scanlan TS, Emery B, Bourdette DN. Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE. J Neuroimmunol. 2021 Mar 15;352:577468. doi: 10.1016/j.jneuroim.2020.577468. Epub 2020 Dec 27. PMID: 33422763; PMCID: PMC8748188. 12: 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. 13: Saponaro F, Sestito S, Runfola M, Rapposelli S, Chiellini G. Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders. Front Med (Lausanne). 2020 Jul 9;7:331. doi: 10.3389/fmed.2020.00331. PMID: 32733906; PMCID: PMC7363807. 14: Grijota-Martínez C, Bárez-López S, Gómez-Andrés D, Guadaño-Ferraz A. MCT8 Deficiency: The Road to Therapies for a Rare Disease. Front Neurosci. 2020 Apr 28;14:380. doi: 10.3389/fnins.2020.00380. PMID: 32410949; PMCID: PMC7198743. 15: Kosar K, Cornuet P, Singh S, Liu S, Nejak-Bowen K. The Thyromimetic Sobetirome (GC-1) Alters Bile Acid Metabolism in a Mouse Model of Hepatic Cholestasis. Am J Pathol. 2020 May;190(5):1006-1017. doi: 10.1016/j.ajpath.2020.01.015. Epub 2020 Mar 20. PMID: 32205094; PMCID: PMC7221298. 16: Hartley MD, Shokat MD, DeBell MJ, Banerji T, Kirkemo LL, Scanlan TS. Pharmacological Complementation Remedies an Inborn Error of Lipid Metabolism. Cell Chem Biol. 2020 May 21;27(5):551-559.e4. doi: 10.1016/j.chembiol.2020.02.008. Epub 2020 Mar 12. PMID: 32169163; PMCID: PMC7245556. 17: Zucchi R. Thyroid Hormone Analogues: An Update. Thyroid. 2020 Aug;30(8):1099-1105. doi: 10.1089/thy.2020.0071. Epub 2020 Apr 7. PMID: 32098589; PMCID: PMC7415871. 18: Hartley MD, Banerji T, Tagge IJ, Kirkemo LL, Chaudhary P, Calkins E, Galipeau D, Shokat MD, DeBell MJ, Van Leuven S, Miller H, Marracci G, Pocius E, Banerji T, Ferrara SJ, Meinig JM, Emery B, Bourdette D, Scanlan TS. Myelin repair stimulated by CNS-selective thyroid hormone action. JCI Insight. 2019 Apr 18;4(8):e126329. doi: 10.1172/jci.insight.126329. PMID: 30996143; PMCID: PMC6538346. 19: Meinig JM, Ferrara SJ, Banerji T, Banerji T, Sanford-Crane HS, Bourdette D, Scanlan TS. Structure-Activity Relationships of Central Nervous System Penetration by Fatty Acid Amide Hydrolase (FAAH)-Targeted Thyromimetic Prodrugs. ACS Med Chem Lett. 2018 Dec 4;10(1):111-116. doi: 10.1021/acsmedchemlett.8b00501. PMID: 30655956; PMCID: PMC6331174. 20: Filgueira CS, Bruno G, Smith ZW, Chua CYX, Ballerini A, Folci M, Gilbert AL, Jain P, Sastry JK, Nehete PN, Shelton KA, Hill LR, Ali A, Youker KA, Grattoni A. Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study. Biomed Microdevices. 2018 Jun 18;20(2):49. doi: 10.1007/s10544-018-0296-2. PMID: 29916059.