Characterization of thyroid hormone receptor alpha (TRalpha)-specific analogs with varying inner- and outer-ring substituents.

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Ocasio CA, Scanlan TS

Characterization of thyroid hormone receptor alpha (TRalpha)-specific analogs with varying inner- and outer-ring substituents.

Bioorg Med Chem. 2008 Jan 15;16(2):762-70. Epub 2007 Oct 18.

PubMed ID
17988877 [ View in PubMed
]
Abstract

Analogs of the TRalpha-specific thyromimetic CO23 were synthesized and analyzed in vitro using competitive binding and transactivation assays. Like CO23, all analogs bind to both thyroid hormone receptor subtypes with about the same affinity; however, modification of CO23 by derivatization of the 3' position of the outer-ring or replacement of the inner-ring iodides with bromides attenuates binding. Despite lacking a preference in binding to TRalpha, all analogs display TRalpha-specificity in transactivation assays using U2OS and HeLa cells. At best, several agonists exhibit an approximately 6-12-fold preference in transactivation when tested with TRalpha in HeLa cells. One analog, CO24, showed in vivo TRalpha-specific action in a tadpole metamorphosis assay.

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