Thyroid hormone (TH) is known to have many beneficial effects on vital organs, but its extrapolation to be used therapeutically has been restricted by the fact that it does have concurrent adverse effects. Recent finding of various
thyroid hormone receptors (TR)
isoforms and their differential pattern of tissue distribution has regained interest in possible use of TH analogues in
therapeutics. These findings were followed by search of compounds with
isoform-specific or tissue-specific action on TR. Studying the structure-activity relationship of TR led to the development of compounds like GC1 and KB141, which preferentially act on the β1
isoform of TR. More recently,
eprotirome was developed and has been studied in humans. It has shown to be effective in
dyslipidemia by the
lipid-lowering action of TH in the liver and also in
obesity. Another compound,
3,5-diiodothyropropionic acid (DITPA), binds to both α- and β-type TRs with relatively low affinity and has been shown to be effective in
heart failure (HF). In postinfarction models of HF and in a pilot clinical study, DITPA increased cardiac performance without affecting the heart rate. TR antagonists like NH3 can be used in
thyrotoxicosis and
cardiac arrhythmias. However, further larger clinical trials on some of these promising compounds and development of newer compounds with increased selectivity is required to achieve higher precision of action and avoid adverse effects seen with TH.