Thyroid hormone analogues: Where do we stand in 2013?

Sunitha Meruvu, Stephen D. Ayers, Glenn Winnier, Paul Webb

Research output: Contribution to journalReview article

18 Scopus citations

Abstract

Thyroid hormones (THs) are important in the development and maintenance of lipid and energy homeostasis. THs act through two closely related TH receptors (TRs α and β), which are conditional transcription factors. Recently, TH analogues or thyromimetics with varying degrees of TR subtype and liver uptake selectivity have been developed. These compounds exert beneficial effects of TH excess states without many undesirable TR-dependent side effects. Several selective TR modulators (STRMs) showed exceptionally promising results in lowering serum cholesterol in preclinical animal models and human clinical studies. Moreover, some first generation STRMs elicit other potentially beneficial effects on obesity, glucose metabolism, and nonalcoholic fatty liver disease (NAFLD). While it was initially thought that STRMs would be an effective long-term therapy to combat elevated cholesterol, possibly in conjunction with another cholesterol-lowering therapy, the statins, three major first generation STRMs failed to progress beyond early phase III human trials. The aim of this review is to discuss how STRMs work, their actions in preclinical animal models and human clinical trials, why they did not progress beyond clinical trials as cholesterol-lowering therapeutics, whether selective TR modulation continues to hold promise for dyslipidemias, and whether members of this drug class could be applied to the treatment of other aspects of metabolic syndrome and human genetic disease.

Original languageEnglish (US)
Pages (from-to)1333-1344
Number of pages12
JournalThyroid
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2013

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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