Gefitinib: Difference between revisions
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< | <StructureSection load='' size='450' side='right' scene='Gefitinib/Gefitinib/1' caption='Gefitinib, also known as Iressa'> | ||
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===Better Known as: Iressa=== | ===Better Known as: Iressa=== | ||
* Marketed By: AstraZeneca & Teva | * Marketed By: AstraZeneca & Teva | ||
* Major Indication: Pancreatic & Small | * Major Indication: Pancreatic & Small Cell Lung [[Cancer]] | ||
* Drug Class: [[EGFR]] Inhibitor | * Drug Class: [[EGFR]] Inhibitor | ||
* Date of FDA Approval (Expiration): 2003 (2013) | * Date of FDA Approval (Expiration): 2003 (2013) | ||
* 2009 Sales: $268 Million | * 2009 Sales: $268 Million | ||
* Importance: It is the first selective inhibitor of Epidermal Growth Factor Receptors approved by the FDA | * Importance: It is the first selective inhibitor of Epidermal Growth Factor Receptors approved by the FDA | ||
* | * See [[Pharmaceutical Drugs]] for more information about other drugs and disorders | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
[[EGFR|Epidermal Growth Factor Receptors]] are overexpressed | [[EGFR|Epidermal Growth Factor Receptors]] are overexpressed in many types of human [[Cancer|carcinomas]] including lung, pancreatic, and breast cancer. This overexpression leads to excessive activation of the anti-apoptotic [[Ras]] signalling cascade, resulting in uncontrolled [[DNA_Replication|DNA synthesis]] and cell proliferation. Studies have revealed that the <scene name='Gefitinib/Kinase/1'>EGFR tyrosine kinase domain</scene> is responsible for activating this Ras signaling cascade. Upon binding ligands like Epidermal Growth Factor, EGFR dimerizes and autophosphorylates several tyrosine residues at its C-terminal domain. It is these phosphorylated tyrosine residues which elicit downstream activation of other signaling proteins and subsequent signaling cascades.<ref>PMID:6090945</ref><ref>PMID:16729045</ref> Gefitinib inhibits the EGFR tyrosine kinase by <scene name='Gefitinib/Bound/1'>binding to the ATP-binding site</scene> located within the kinase domain. Residues Lys 745, Leu 788, Ala 743, Thr 790, Gln 791, Met 193, Pro 794, Gly 796, Asp 800, Ser 719, Glu 762, & Met 766 tightly bind the inhibitor. Unable to bind ATP, EGFR is incapable of autophosphorylating its C-terminal tyrosines, and the uncontrolled cell-proliferation signal is terminated.<ref>PMID:15284455</ref> | ||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
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{{:Tyrosine Kinase Inhibitor Pharmacokinetics}} | |||
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===References=== | ===References=== | ||
<references/> | <references/> | ||
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