Rosiglitazone: Difference between revisions

===Mechanism of Action===

Rosiglitazone is a selective agonist for <scene name='Rosiglitazone/Ppar/1'>Peroxisome Proliferator-Activated Receptor Gamma </scene> ([[PPAR]]). Unliganded PPAR forms a complex with various co-repressors which possess histone deacetylation activity, maintaining tight chromatin structure and preventing gene transcription. This complex is released upon ligand binding (typical ligands are lipids), allowing various co-activators and co-activator-associated proteins to be recruited. Rosiglitazone functions by by binding to the active site of PPARγ, causing the release of co-repressors and activation of the receptor. Activation of PPAR results in transcription of [[Molecular Playground/Insulin|insulin]] responsive genes involved in the control of glucose production, transport and utilization. This explains why the glitazones are referred to as "insulin sensitizers." Rosiglitazone occupies roughly 40% of the LBD. It assumes a U-shaped conformation with the TZD head group <scene name='Rosiglitazone/Rosiglitazone_binding/3'>forming a number of interactions </scene>that stabilize the agonist. Rosiglitazone forms hydrogen bond interactions with H323 and H449 and its TZD group, the sulfur atom of the TZD occupies a hydrophobic pocket formed by Phe363, Glu286, Phe282, Leu330, Ile326 and Leu469, and the central benzene ring occupies a pocket formed by Cys285 and Met364 <ref>PMID:9744270</ref>

===Pharmacokinetics===

===Effectiveness===