{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:10:41Z","timestamp":1792080641999,"version":"4.4.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>The development of thyroid hormone (TH) analogues was prompted by the attempt to exploit the effects of TH on lipid metabolism, avoiding cardiac thyrotoxicosis. Analysis of the relative distribution of the \u03b1 and \u03b2 subtypes of nuclear TH receptors (TR\u03b1 and TR\u03b2) showed that TR\u03b1 and TR\u03b2 are responsible for cardiac and metabolic responses, respectively. Therefore, analogues with TR\u03b2 selectivity were developed, and four different compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344\/VK2809, and MGL-3196 (resmetirom). Each of these compounds was able to reduce low-density lipoprotein cholesterol, but a phase 3 trial with eprotirome was interrupted because of a significant increase in liver enzymes and the contemporary report of cartilage side effects in animals. As a consequence, the other projects were terminated as well. However, in recent years, TR\u03b2 agonists have raised new interest for the treatment of nonalcoholic fatty liver disease (NAFLD). After obtaining excellent results in experimental models, clinical trials have been started with MGL-3196 and VK2809, and the initial reports are encouraging. Sobetirome turned out to be effective also in experimental models of demyelinating disease. Aside TR\u03b2 agonists, TH analogues include some TH metabolites that are biologically active on their own, and their synthetic analogues. 3,5,3\u2032-triiodothyroacetic acid has already found clinical use in the treatment of some cases of TH resistance due to TR\u03b2 mutations, and interesting results have recently been reported in patients with the Allan\u2013Herndon\u2013Dudley syndrome, a rare disease caused by mutations in the TH transporter MCT8. 3,5-diiodothyronine (T2) has been used with success in rat models of dyslipidemia and NAFLD, but the outcome of a clinical trial with a synthetic T2 analogue was disappointing. 3-iodothyronamine (T1AM) is the last entry in the group of active TH metabolites. Promising results have been obtained in animal models of neurological injury induced by \u03b2-amyloid or by convulsive agents, but no clinical data are available so far.<\/jats:p>","DOI":"10.1089\/thy.2020.0071","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T03:43:32Z","timestamp":1582688612000},"page":"1099-1105","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":86,"title":["Thyroid Hormone Analogues: An Update"],"prefix":"10.1177","volume":"30","author":[{"given":"Riccardo","family":"Zucchi","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.143"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00250"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.205"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00427"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0113"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0178"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00182"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-02018-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm2004706"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.04.006"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.04.003"},{"key":"e_1_3_3_13_2","unstructured":"Lin VW Klepp HM Hanley RM. 2008 Sobetirome is a TR\u03b2- and liver-selective thyromimetic that can affect substantial LDL-C lowering without significant changes in heart rate or the thyroid axis in euthyroid men [abstract]. 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