Journal
ACS CHEMICAL BIOLOGY
Volume 1, Issue 9, Pages 585-593Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cb600311v
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- NIDDK NIH HHS [DK-52798] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK052798, R56DK052798] Funding Source: NIH RePORTER
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Thyroid hormone is a classical endocrine signaling molecule that regulates a diverse array of physiological processes ranging from energy metabolism to cardiac performance. The active form of thyroid hormone, 3,5,3'-triiodo-L-thyronine or T-3, exerts many of its actions through its receptor, the thyroid hormone receptor (TR), of which there are two subtypes for two isoforms: TR alpha(1), TR alpha(2), TR beta(1), and TR beta(2). Although TR isoforms, with the exception of TR beta(2), are expressed in all tissues, they display different patterns of expression in different tissues, giving rise to tissue-specific isoform actions. Currently, several TR beta-selective agonists have been developed; however, TR beta-selective agonists have remained elusive. Herein, we report the synthesis and biological evaluation of CO23, the first potent thyromimetic with TR alpha-specific effects in vitro and in vivo.
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