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The nuclear receptor-coactivator interaction surface as a target for peptide antagonists of the peroxisome proliferator-activated receptors.

Mol. Endocrinol.. 2007; 
MettuNiharika B,StanleyThomas B,DwyerMary A,JansenMichelle S,AllenJohn E,HallJulie M,McDonnellDona
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摘要

The peroxisome proliferator-activated receptors (PPARalpha, PPARdelta, and PPARgamma) constitute a family of nuclear receptors that regulates metabolic processes involved in lipid and glucose homeostasis. Although generally considered to function as ligand-regulated receptors, all three PPARs exhibit a high level of constitutive activity that may result from their stimulation by intracellularly produced endogenous ligands. Consequently, complete inhibition of PPAR signaling requires the development of inverse agonists. However, the currently available small molecule antagonists for the PPARs function only as partial agonists, or their efficacy is not sufficient to inhibit the constitutive activity o... More

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