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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* 2009 (2006) Sales: $400 Million ($2.5 Billion)<ref>http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=AVANDIA</ref> | * 2009 (2006) Sales: $400 Million ($2.5 Billion)<ref>http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=AVANDIA</ref> | ||
* Importance: Once the best selling Diabetes treatment in the world. Lawsuits and legal action being pursued against GlaxoSmithKline for manipulation of clinical data upon which Avandia was approved with regards to its side effect profile. | * Importance: Once the best selling Diabetes treatment in the world. Lawsuits and legal action being pursued against GlaxoSmithKline for manipulation of clinical data upon which Avandia was approved with regards to its side effect profile. | ||
* | * See [[Pharmaceutical Drugs]] for more information about other drugs and disorders | ||
===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=== | ||
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{{:Glitazone Pharmacokinetics}} | |||
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</table> | |||
===Effectiveness=== | ===Effectiveness=== | ||