Erlotinib: Difference between revisions
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< | <StructureSection load='' size='450' side='right' scene='Erlotinib/Erlotinib/1' caption='Erlotinib, also known as Tarceva'> | ||
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===Better Known as: Tarceva=== | ===Better Known as: Tarceva=== | ||
* Marketed By: Genentech, OSI Pharmaceutials, & Roche | * Marketed By: Genentech, OSI Pharmaceutials, & Roche | ||
* Major Indication: Pancreatic & Small | * Major Indication: Pancreatic & Small Cell Lung [[Cancer]] | ||
* Drug Class: [[EGFR]] Inhibitor | * Drug Class: [[EGFR]] Inhibitor | ||
* Date of FDA Approval (Expiration): 2005 (2020) | * Date of FDA Approval (Expiration): 2005 (2020) | ||
* 2009 Sales: $1.2 Billion | * 2009 Sales: $1.2 Billion | ||
* Importance: It is one of the best selling and most effective treatments for several types of cancer. It is an improved version of [[Iressa]]. | * Importance: It is one of the best selling and most effective treatments for several types of cancer. It is an improved version of [[Iressa]]. | ||
* | * See [[Pharmaceutical Drugs]] for more information about other drugs and disorders | ||
* See also [[Journal:JBSD:26|Investigation on the Site-Selective Binding of Bovine Serum Albumin by Erlotinib Hydrochloride]] | |||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
[[EGFR|Epidermal Growth Factor Receptors]] are overexpressed in many types of human [[Cancer|carcinomas]] including lung, pancreatic, and breast cancer, and are often mutated. 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='Erlotinib/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. Upon phosphorylation, EGFR undergoes a conformational change, revealing an additional binding site capable of eliciting downstream activation of other signaling proteins.<ref>PMID:6090945</ref><ref>PMID:16729045</ref> Erlotinib inhibits the EGFR tyrosine kinase by <scene name='Erlotinib/Bound/1'>binding to the ATP-binding site</scene> located within the kinase domain. EGFR uses residues Asp 831, Lys 721, Thr 766, Leu 820, Gly 772, Phe 771, Leu 694, Pro 770, Met 769, Leu 768, Gln 767 & Ala 719 to 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><ref>PMID:11129168</ref> | [[EGFR|Epidermal Growth Factor Receptors]] are overexpressed in many types of human [[Cancer|carcinomas]] including lung, pancreatic, and breast cancer, and are often mutated. 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='Erlotinib/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. Upon phosphorylation, EGFR undergoes a conformational change, revealing an additional binding site capable of eliciting downstream activation of other signaling proteins.<ref>PMID:6090945</ref><ref>PMID:16729045</ref> Erlotinib inhibits the EGFR tyrosine kinase by <scene name='Erlotinib/Bound/1'>binding to the ATP-binding site</scene> located within the kinase domain. EGFR uses residues Asp 831, Lys 721, Thr 766, Leu 820, Gly 772, Phe 771, Leu 694, Pro 770, Met 769, Leu 768, Gln 767 & Ala 719 to 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><ref>PMID:11129168</ref> | ||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
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{{:Tyrosine Kinase Inhibitor Pharmacokinetics}} | |||
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===References=== | ===References=== | ||
<references/> | <references/> | ||
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