Rosiglitazone: Difference between revisions
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< | <StructureSection load='' size='340' side='right' caption='Rosiglitazone, also known as Avandia' scene='Rosiglitazone/Rosiglitazon/1'> | ||
===Better Known as: Avandia=== | ===Better Known as: Avandia=== | ||
* Marketed By: GlaxoSmithKline (No Longer Marketed)<br /> | * Marketed By: GlaxoSmithKline (No Longer Marketed)<br /> | ||
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===Mechanism of Action=== | ===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> | 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> | ||
</StructureSection> | |||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%"> | <table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%"> | ||