Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight.
The current report describes progress in development of a selective thyroid hormone receptor modulator, GC-1. This compound binds selectively to the beta-isoform of the thyroid hormone receptor, and its uptake into the heart is relatively low. Studies in rats, mice and monkeys show that GC-1 lowers cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin, a compound that blocks HMG-CoA reductase. GC-1 also decreases plasma levels of triglyceride and lipoprotein (a), and induces loss of fat. These effects can be observed under conditions where there is either no or minimal effect on heart rate, and no detectable loss of muscle. Although more study is required, compounds of this class deserve further investigation for treating lipid disorders and obesity.
Baxter
John D
JD
Diabetes Center and Department of Medicine, University of California-San Francisco, San Francisco, CA 94143-0540, USA. JBaxter918@aol.com
Webb
Paul
P
Grover
Gary
G
Scanlan
Tom S
TS
D000085:Acetates / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood; D010636:Phenols / Q000493:pharmacokinetics / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D037021:Thyroid Hormone Receptors alpha / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000187:drug effects; D013963:Thyroid Hormones / Q000009:adverse effects / Q000494:pharmacology* / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
D000085:Acetates; D000924:Anticholesteremic Agents; C413355:GC 1 compound; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D010636:Phenols; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D002784:Cholesterol