| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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Purity: ≥98%
Sobetirome (GC-1; QRX-431) is a novel, potent and selective agonist of the thyroid hormone receptor-beta (TRβ) that lowers cholesterol. It binds to TRβ-1 selectively, with an EC50 of 0.16 μM, to produce its effect. In osteoblast-like cells derived from mice and rats, sobetirome suppresses proliferation but promotes differentiation and the expression of TR beta mRNA. The theory that sobetirome would lower cholesterol by activating liver TRbeta without promoting cardiac function by activating heart TRalpha was based on the receptor's selectivity, which allows sobetirome to bind to and activate TRbeta over TRalpha. Based on multiple animal models demonstrating tissue selective thyromimetic properties, sobetirome was developed clinically as a novel agent to lower cholesterol.
| Targets |
TRβ-1 (EC50 = 0.16 μM); TRα-1 (EC50 = 0.58 μM)
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| ln Vivo |
Sobetirome (GC-1) is a selective agonist for the thyroid hormone receptor β (TRβ) and liver uptake. In euthyroid mice, sobetirome (48 nmol/kg) lowers levels of very low-density lipoprotein (VLDL) triglycerides and high-density lipoprotein (HDL) cholesterol. In hypercholesterolemic mice, sobetirome lowers triglyceride and HDL cholesterol levels. In hypercholesterolemic mice, sobetirome stimulates the synthesis of bile acid and increases the number of HDL receptors in the liver[2]. Treatment with 10× Sobetirome (GC-1) causes only a 21% (1.7 g) increase in fat mass, while treatment with 20× Sobetirome (GC-1) causes a 20% (1.3 g) decrease in fat mass[3].
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| Animal Protocol |
Animals:** 3-month-old male C57BL/6 mice were used. They were kept in standardized conditions with free access to water and normal chow. [2]
- **Drug Preparation and Administration:** GC-1 was dissolved in 20% DMSO or propylene glycol and administered via daily intraperitoneal (i.p.) injection at 9:00 a.m. for 8 days. Control mice received vehicle only. [2] - **Dose-Response Study:** Nine groups of six mice were treated with vehicle, or 5.4, 24, 48, and 97 nmol/kg/day of either T3 or GC-1. [2] - **Diet-Induced Hypercholesterolemia Study:** One group of seven mice was given no additional supplementation. Three groups of seven mice received a diet containing 10% corn oil and 2% cholesterol (cholesterol diet). Three groups of seven mice received a diet containing 10% corn oil, 2% cholesterol, and 0.5% cholic acid (cholic acid diet). For each diet, one group was treated with vehicle, one with GC-1 (97 nmol/kg/day), and one with T3 (97 nmol/kg/day). [2] - **Bile Acid Excretion Study:** Three groups of five chow-fed mice were treated with vehicle, 48 nmol/kg/day of GC-1, or T3 for 5 days. Feces were collected group-wise 24 hours before treatment and during the last 24 hours of the experiment. [2] - **Tissue Collection:** Food was withdrawn 5 hours before sacrifice. Blood was drawn by cardiac puncture under light isoflurane anesthesia. Animals were killed by cervical dislocation. Livers were immediately frozen in liquid nitrogen. [2] |
| References |
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| Additional Infomation |
Sobetirome is a diarylmethane compound. It is a liver-selective analog of the β1 subtype of thyroid hormone receptor, possessing lipid-lowering and anti-atherosclerotic activities. In animal models, Sobetirome lowers blood lipids and cholesterol levels, and stimulates reverse cholesterol transport, promoting the reverse transport of cholesterol from atherosclerotic macrophages back to the liver for excretion. In human trials, Sobetirome lowers plasma LDL cholesterol and plasma triglyceride levels; its liver-selective action helps avoid many of the side effects common to other thyroid hormone analogs.
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| Molecular Formula |
C20H24O4
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|---|---|
| Molecular Weight |
328.40216
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| Exact Mass |
328.167
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| Elemental Analysis |
C, 73.15; H, 7.37; O, 19.49
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| CAS # |
211110-63-3
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| Related CAS # |
211110-63-3
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| PubChem CID |
9862248
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| Appearance |
White to yellow solid powder
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| Density |
1.152g/cm3
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| Boiling Point |
510.156ºC at 760 mmHg
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| Flash Point |
178.945ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.575
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| LogP |
4.186
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
396
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(O)COC1=CC(C)=C(CC2=CC=C(O)C(C(C)C)=C2)C(C)=C1
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| InChi Key |
QNAZTOHXCZPOSA-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-[4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenoxy]acetic acid
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| Synonyms |
Sobetirome; GC-1; GC 1; GC1; QRX-431; QRX431; QRX 431
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~304.5 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.61 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0451 mL | 15.2253 mL | 30.4507 mL | |
| 5 mM | 0.6090 mL | 3.0451 mL | 6.0901 mL | |
| 10 mM | 0.3045 mL | 1.5225 mL | 3.0451 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01787578 | Withdrawn | Drug: Sobetirome | X-Linked Adrenoleukodystrophy Adrenomyeloneuropathy |
Thomas S. Scanlan | April 2013 | Phase 1 |
| NCT03196765 | Withdrawn | Drug: Sobetirome (NV1205) |
X-Linked Adrenoleukodystrophy | NeuroVia, Inc. | August 2018 | Phase 1 Phase 2 |
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