Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges

The association between thyroid hormone status and plasma levels of low-density lipoprotein cholesterol has raised the awareness for the development of thyroid hormone mimetics as lipid-lowering agents. The discovery of the two main types of thyroid hormone receptors (α and β) as well as the development of novel combinatorial chemistry providing organ specificity has drastically improved the selectivity of these compounds. In the past decades, several thyroid hormone mimetics have been investigated with the purpose of lowering low-density lipoprotein cholesterol levels. However, until now, none of the thyromimetics reached the stage of completing a phase III clinical trial without deleterious side effects. Here, we review the currently available literature on thyromimetics investigated for the treatment of dyslipidemia, their rise, their downfall and the challenges for the development of novel agents.