| Literature DB >> 21986665 |
Shengchen Lin1, Ying Han, Yuzhe Shi, Hui Rong, Songyang Zheng, Shikan Jin, Shu-Yong Lin, Sheng-Cai Lin, Yong Li.
Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPARγ agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPARγ target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPARγ ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPARγ ligands in the treatment of insulin resistance.Entities:
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Year: 2011 PMID： 21986665 PMCID： PMC3257359 DOI： 10.1038/cr.2011.162
Source DB: PubMed Journal: Cell Res ISSN： 1001-0602 Impact factor: 25.617