Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight

Trends Endocrinol Metab. 2004 May-Jun;15(4):154-7. doi: 10.1016/j.tem.2004.03.008.


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.

Publication types

  • Review

MeSH terms

  • Acetates / pharmacokinetics
  • Acetates / pharmacology*
  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Body Weight / drug effects
  • Cholesterol / blood*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lipoproteins / blood
  • Phenols / pharmacokinetics
  • Phenols / pharmacology*
  • Signal Transduction / drug effects*
  • Thyroid Hormone Receptors alpha / drug effects
  • Thyroid Hormone Receptors beta / drug effects
  • Thyroid Hormones / adverse effects
  • Thyroid Hormones / pharmacology*
  • Thyroid Hormones / physiology
  • Weight Loss / drug effects


  • Acetates
  • Anticholesteremic Agents
  • GC 1 compound
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins
  • Phenols
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta
  • Thyroid Hormones
  • Cholesterol