Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms.

ABSTRACT:

Background

Thyroid receptors, TRalpha and TRbeta, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TRbeta isoform activation, TRalpha activation affects heart rates. Therefore, beta-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin (Lipitor(c)) in studies in rats, mice and monkeys.

Results

To investigate GC-1 specificity, we solved crystal structu

SUBMITTER: Bleicher L 

PROVIDER: S-EPMC2275733 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature