Design and characterization of a thyroid hormone receptor alpha (TRalpha)-specific agonist.

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Ocasio CA, Scanlan TS

Design and characterization of a thyroid hormone receptor alpha (TRalpha)-specific agonist.

ACS Chem Biol. 2006 Oct 24;1(9):585-93.

PubMed ID
17168554 [ View in PubMed
]
Abstract

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 .

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
LiothyronineThyroid hormone receptor alphaKd (nM)0.058N/AN/ADetails
LiothyronineThyroid hormone receptor alphaEC 50 (nM)2.4N/AN/ADetails
LiothyronineThyroid hormone receptor betaKd (nM)0.081N/AN/ADetails
LiothyronineThyroid hormone receptor betaEC 50 (nM)11N/AN/ADetails
LiothyronineThyroid hormone receptor betaEC 50 (nM)2.4N/AN/ADetails