Cell lines

Rat brown adipocytes.

Preparation method

Soluble in DMSO >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

0.2-200 nM; 24 h.

Applications

In rat brown adipocytes, GC-1 increases Ucp1 mRNA expression and D2 activity stimulated by adrenergic. Also, GC-1 (10 nM) further increases cAMP production induced by NE or BRL 37344.

Animal models

Hypothyroid mice.

Dosage form

1.8-49.33 ng/g BW. day; 4 weeks of daily ip injection.

Applications

In hypothyroid mice, GC-1 increases heart rate and maximum speeds of contraction (dP/dtmax). GC-1 increases dP/dtmax and arterial pressure by 17% and 39%, respectively.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Sobetirome (3,5-dimethyl-4[(4'-hydroxy-3'-isopropylbenzyl)-phenoxy] acetic acid, also known as GC-1 and QRX-431, is a member of a class of compounds known as selective thyromimetics.It was firstly developed by Thomas Scanlan’s group at the University of California-San Francisco (UCSF) in 1995¹.

In cholesterol-fed rats, sobetirome was shown to lower plasma cholesterol in a dose-dependent manner by up to 75% of untreated controls. In hypercholesterolemic mice, sobetirome was failed to induce LDL receptor mRNA expression. In different mouse models, sobetirome and T-0681 were shown to promote bile acid production and biliary sterol secretion. In cynomolgus monkeys, sobetirome was shown to reduce plasma cholesterol in a dose-dependent manner by up to 30%. Both sobetirome and T-0681 were shown to increase hepatic expression of the HDL receptor (scavenger receptor-BI, SR-BI) in animals.

In Phase I clinical trials, Sobetirome was shown to be generally well tolerated at all doses studied and proof of the therapeutic concept of cholesterol lowering was clearly demonstrated¹.

References:
1. Tancevski I, Demetz E, Eller P. Sobetirome: a selective thyromimetic for the treatment of dyslipidemia. Recent Pat Cardiovasc Drug Discov. 2011 Jan;6(1):16-9.