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.

Physicochemical Properties

Molecular Formula	C20H24O4
Molecular Weight	328.40216
Exact Mass	328.167
Elemental Analysis	C, 73.15; H, 7.37; O, 19.49
CAS #	211110-63-3
Related CAS #	211110-63-3
PubChem CID	9862248
Appearance	White to yellow solid powder
Density	1.152g/cm3
Boiling Point	510.156ºC at 760 mmHg
Flash Point	178.945ºC
Vapour Pressure	0mmHg at 25°C
Index of Refraction	1.575
LogP	4.186
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	6
Heavy Atom Count	24
Complexity	396
Defined Atom Stereocenter Count	0
SMILES	O=C(O)COC1=CC(C)=C(CC2=CC=C(O)C(C(C)C)=C2)C(C)=C1
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)
Chemical Name	2-[4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenoxy]acetic acid
Synonyms	Sobetirome; GC-1; GC 1; GC1; QRX-431; QRX431; QRX 431
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	TRβ-1 (EC50 = 0.16 μM); TRα-1 (EC50 = 0.58 μM)
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].
References	[1]. Bacterial biosensors for screening isoform-selective ligands for human thyroid receptors α-1 and β-1. FEBS Open Bio. 2012 Aug 15;2:247-53. [2]. Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice. Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10297-302. [3]. Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats. J Endocrinol. 2007 Apr;193(1):21-9.
Additional Infomation	Sobetirome is a diarylmethane. Sobetirome is a thyroid hormone receptor isoform beta-1 liver-selective analog with antilipidemic and antiatherosclerotic activity. In animal models sobetirome reduced serum lipids, decreased cholesterol levels, and stimulated steps of reverse cholesterol transport, which promotes the reverse transport of cholesterol from atherogenic macrophages back to the liver for excretion. In humans, sobetirome lowered plasma LDL cholesterol and reduced plasma triglycerides, while its liver-selective activity helped avoid the side effects seen with many other thyromimetic agents.

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~304.5 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.