Journal article
Jordan J Devereaux, S. Ferrara, Tania Banerji, Andrew T. Placzek, T. Scanlan
ChemMedChem, 2016
ChemMedChem, 2016
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APA
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Devereaux, J. J., Ferrara, S., Banerji, T., Placzek, A. T., & Scanlan, T. (2016). Increasing Thyromimetic Potency through Halogen Substitution. ChemMedChem.
Chicago/Turabian
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Devereaux, Jordan J, S. Ferrara, Tania Banerji, Andrew T. Placzek, and T. Scanlan. “Increasing Thyromimetic Potency through Halogen Substitution.” ChemMedChem (2016).
MLA
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Devereaux, Jordan J., et al. “Increasing Thyromimetic Potency through Halogen Substitution.” ChemMedChem, 2016.
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@article{jordan2016a,
title = {Increasing Thyromimetic Potency through Halogen Substitution},
year = {2016},
journal = {ChemMedChem},
author = {Devereaux, Jordan J and Ferrara, S. and Banerji, Tania and Placzek, Andrew T. and Scanlan, T.}
}
Abstract
Sobetirome is one of the most studied thyroid hormone receptor β (TRβ)‐selective thyromimetics in the field due to its excellent selectivity and potency. A small structural change—replacing the 3,5‐dimethyl groups of sobetirome with either chlorine or bromine—produces significantly more potent compounds, both in vitro and in vivo. These halogenated compounds induce transactivation of a TRβ‐mediated cell‐based reporter with an EC50 value comparable to that of T3, access the central nervous system (CNS) at levels similar to their parent, and activate an endogenous TR‐regulated gene in the brain with an EC50 value roughly five‐fold lower than that of sobetirome. Previous studies suggest that this apparent increase in affinity can be explained by halogen bonding between the ligand and a backbone carbonyl group in the receptor. This makes the new analogues potential candidates for treating CNS disorders that may respond favorably to thyroid‐hormone‐stimulated pathways.
