Endocrinol Metab.  2024 Apr;39(2):285-287. 10.3803/EnM.2024.203.

Selective Agonists of Thyroid Hormone Receptor Beta: Promising Tools for the Treatment of Nonalcoholic Fatty Liver Disease

• Cho SW

• KMID: 2554633
• DOI: http://doi.org/10.3803/EnM.2024.203

Reference

1. Tancevski I, Rudling M, Eller P. Thyromimetics: a journey from bench to bed-side. Pharmacol Ther. 2011; 131:33–9.

2. Berkenstam A, Kristensen J, Mellstrom K, Carlsson B, Malm J, Rehnmark S, et al. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. Proc Natl Acad Sci U S A. 2008; 105:663–7.

3. Scanlan TS. Sobetirome: a case history of bench-to-clinic drug discovery and development. Heart Fail Rev. 2010; 15:177–82.

4. Hartley MD, Kirkemo LL, Banerji T, Scanlan TS. A thyroid hormone-based strategy for correcting the biochemical abnormality in X-linked adrenoleukodystrophy. Endocrinology. 2017; 158:1328–38.

5. Sjouke B, Langslet G, Ceska R, Nicholls SJ, Nissen SE, Ohlander M, et al. Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, doubleblind, placebo-controlled phase 3 study. Lancet Diabetes Endocrinol. 2014; 2:455–63.

6. Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2019; 394:2012–24.

7. Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024; 390:497–509.

8. Erion MD, Cable EE, Ito BR, Jiang H, Fujitaki JM, Finn PD, et al. Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index. Proc Natl Acad Sci U S A. 2007; 104:15490–5.

9. Kelly MJ, Pietranico-Cole S, Larigan JD, Haynes NE, Reynolds CH, Scott N, et al. Discovery of 2-[3,5-dichloro-4-(5- isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5- dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL3196), a highly selective thyroid hormone receptor β agonist in clinical trials for the treatment of dyslipidemia. J Med Chem. 2014; 57:3912–23.

10. Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, et al. American Association of Clinical Endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022; 28:528–62.

11. ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. Addendum. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of care in diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S49-S67. Diabetes Care. 2023; 46:1718–20.

12. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023; 77:1797–835.

13. Wirth EK, Puengel T, Spranger J, Tacke F. Thyroid hormones as a disease modifier and therapeutic target in nonalcoholic steatohepatitis. Expert Rev Endocrinol Metab. 2022; 17:425–34.

14. Lonardo A, Ballestri S, Mantovani A, Nascimbeni F, Lugari S, Targher G. Pathogenesis of hypothyroidism-induced NAFLD: evidence for a distinct disease entity? Dig Liver Dis. 2019; 51:462–70.