TY - JOUR
T1 - Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms
AU - Bleicher, Lucas
AU - Aparicio, Ricardo
AU - Nunes, Fabio M.
AU - Martinez, Leandro
AU - Gomes Dias, Sandra M.
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.
AU - Baxter, John D.
AU - Webb, Paul
AU - Skaf, Munir S.
AU - Polikarpov, Igor
N1 - Funding Information:
We thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grants #06/00182-8), the Conselho Nacional de Desenvolvi-mento Científico e Tecnológico (CNPq, grants #479800/2004-9 to MSS and #473875/2003-9 to IP), the Coordenação de Aperfeiçoamento de Pessoal do Nível Superior (CAPES), and the National Institutes of Health (DK41482 and DK64148 to JDB) for financial support. JDB has proprietary interests in, and serves as a consultant and Deputy Director to Karo Bio AB, which has commercial interests in this area of research. The 3D protein figures were produced with Pymol [45].
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - 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
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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U2 - 10.1186/1472-6807-8-8
DO - 10.1186/1472-6807-8-8
M3 - Article
C2 - 18237438
AN - SCOPUS:43049106192
VL - 8
JO - BMC Structural Biology
JF - BMC Structural Biology
SN - 1472-6807
M1 - 8
ER -