Ocasio Cory A, Scanlan Thomas S
Chemistry and Chemical Biology Graduate Program and the Department of Pharmaceutical Chemistry, University of California-San Francisco, 600 16th Street, San Francisco, California 94143-2280, USA.
ACS Chem Biol. 2006 Oct 24;1(9):585-93. doi: 10.1021/cb600311v.
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: TRalpha 1 , TRalpha 2 , TRbeta 1 , and TRbeta 2 . Although TR isoforms, with the exception of TRbeta 2 , are expressed in all tissues, they display different patterns of expression in different tissues, giving rise to tissue-specific isoform actions. Currently, several TRbeta-selective agonists have been developed; however, TRalpha-selective agonists have remained elusive. Herein, we report the synthesis and biological evaluation of CO23, the first potent thyromimetic with TRalpha-specific effects in vitro and in vivo .
甲状腺激素是一种经典的内分泌信号分子，可调节从能量代谢到心脏功能等一系列生理过程。甲状腺激素的活性形式3,5,3'-三碘-L-甲状腺原氨酸（T3）通过其受体甲状腺激素受体（TR）发挥许多作用，TR有两种亚型对应两种同工型：TRα1、TRα2、TRβ1和TRβ2。尽管除TRβ2外，TR同工型在所有组织中均有表达，但它们在不同组织中表现出不同的表达模式，从而产生组织特异性同工型作用。目前，已经开发出几种TRβ选择性激动剂；然而，TRα选择性激动剂仍然难以捉摸。在此，我们报告了CO23的合成及生物学评价，它是首个在体外和体内具有TRα特异性作用的强效拟甲状腺素。
