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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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Drug Therapy01:28

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Thyroid Hormone Analogues: An Update.

Riccardo Zucchi1

  • 1Department of Pathology, University of Pisa, Pisa, Italy.

Thyroid : Official Journal of the American Thyroid Association
|February 27, 2020
PubMed
Summary
This summary is machine-generated.

Thyroid hormone (TH) analogues targeting TRβ receptors show promise for treating nonalcoholic fatty liver disease and demyelinating diseases. While early trials faced setbacks, newer compounds like resmetirom and VK2809 are showing encouraging results in clinical studies.

Keywords:
3,5-diiodothyronine3-iodothyronamineTH analogueseprotiromeresmetiromsobetirometriac

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Area of Science:

  • Endocrinology and Metabolic Diseases
  • Pharmacology and Drug Development

Background:

  • Thyroid hormone (TH) analogues were developed to leverage TH's lipid-lowering effects while minimizing cardiac side effects.
  • Nuclear TH receptors (TRα and TRβ) mediate distinct physiological responses; TRβ is primarily linked to metabolic functions.

Purpose of the Study:

  • To review the development and therapeutic potential of TRβ-selective thyroid hormone analogues.
  • To explore the application of these analogues in treating nonalcoholic fatty liver disease (NAFLD) and other conditions.

Main Methods:

  • Analysis of TRα and TRβ receptor distribution and function.
  • Development and clinical investigation of TRβ-selective compounds (GC-1, KB-2115, MB07344/VK2809, MGL-3196).
  • Evaluation of TH metabolites (3,5,3'-triiodothyroacetic acid, 3,5-diiodothyronine, 3-iodothyronamine) and their analogues.

Main Results:

  • TRβ agonists demonstrated efficacy in reducing low-density lipoprotein cholesterol, but early trials were halted due to safety concerns (liver enzymes, cartilage effects).
  • Recent clinical trials with MGL-3196 (resmetirom) and VK2809 for NAFLD show promising initial results.
  • Sobetirome (GC-1) showed efficacy in experimental models of demyelinating disease; TH metabolites like 3,5,3'-triiodothyroacetic acid are used clinically for TH resistance and Allan-Herndon-Dudley syndrome.

Conclusions:

  • TRβ agonists are regaining interest for NAFLD treatment, with ongoing trials yielding encouraging outcomes.
  • TH analogues and metabolites offer diverse therapeutic avenues, including metabolic disorders, demyelinating diseases, and rare genetic conditions.
  • Further research and clinical evaluation are warranted to fully establish the safety and efficacy of these compounds.