Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Lucas Bleicher; Ricardo Aparicio; Fabio M. Nunes; Leandro Martinez; Sandra M. Gomes Dias; Ana Carolina Migliorini Figueira; Maria Auxiliadora Morim Santos; Walter H. Venturelli; Rosangela Da Silva; Paulo Marcos Donate; Francisco A.R. Neves; Luiz A. Simeoni; John D. Baxter; Paul Webb; Munir S. Skaf; Igor Polikarpov

doi:10.1186/1472-6807-8-8

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Lucas Bleicher, Ricardo Aparicio, Fabio M. Nunes, Leandro Martinez, Sandra M. Gomes Dias, Ana Carolina Migliorini Figueira, Maria Auxiliadora Morim Santos, Walter H. Venturelli, Rosangela Da Silva, Paulo Marcos Donate, Francisco A.R. Neves, Luiz A. Simeoni, John D. Baxter, Paul Webb, Munir S. Skaf, Igor Polikarpov

Academic Institute

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Background. Thyroid receptors, TRα and TRβ, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TRβ isoform activation, TRα activation affects heart rates. Therefore, β-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin (Lipitor

Original language	English (US)
Article number	8
Journal	BMC Structural Biology
Volume	8
DOIs	https://doi.org/10.1186/1472-6807-8-8
State	Published - 2008

ASJC Scopus subject areas

Structural Biology

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Bleicher, L., Aparicio, R., Nunes, F. M., Martinez, L., Gomes Dias, S. M., Figueira, A. C. M., Santos, M. A. M., Venturelli, W. H., Da Silva, R., Donate, P. M., Neves, F. A. R., Simeoni, L. A., Baxter, J. D., Webb, P., Skaf, M. S., & Polikarpov, I. (2008). Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms. BMC Structural Biology, 8, [8]. https://doi.org/10.1186/1472-6807-8-8

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms. / Bleicher, Lucas; Aparicio, Ricardo; Nunes, Fabio M.; Martinez, Leandro; Gomes Dias, Sandra M.; Figueira, Ana Carolina Migliorini; Santos, Maria Auxiliadora Morim; Venturelli, Walter H.; Da Silva, Rosangela; Donate, Paulo Marcos; Neves, Francisco A.R.; Simeoni, Luiz A.; Baxter, John D.; Webb, Paul; Skaf, Munir S.; Polikarpov, Igor.

In: BMC Structural Biology, Vol. 8, 8, 2008.

Research output: Contribution to journal › Article › peer-review

Bleicher, Lucas ; Aparicio, Ricardo ; Nunes, Fabio M. ; Martinez, Leandro ; Gomes Dias, Sandra M. ; Figueira, Ana Carolina Migliorini ; Santos, Maria Auxiliadora Morim ; Venturelli, Walter H. ; Da Silva, Rosangela ; Donate, Paulo Marcos ; Neves, Francisco A.R. ; Simeoni, Luiz A. ; Baxter, John D. ; Webb, Paul ; Skaf, Munir S. ; Polikarpov, Igor. / Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms. In: BMC Structural Biology. 2008 ; Vol. 8.

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abstract = "Background. Thyroid receptors, TRα and TRβ, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TRβ isoform activation, TRα activation affects heart rates. Therefore, β-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin (Lipitor",

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AU - Figueira, Ana Carolina Migliorini

AU - Santos, Maria Auxiliadora Morim

AU - Venturelli, Walter H.

AU - Da Silva, Rosangela

AU - Donate, Paulo Marcos

AU - Neves, Francisco A.R.

AU - Simeoni, Luiz A.

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AB - Background. Thyroid receptors, TRα and TRβ, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TRβ isoform activation, TRα activation affects heart rates. Therefore, β-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin (Lipitor

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Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Abstract

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