Lapatinib: Difference between revisions
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<StructureSection load='' size='450' side='right' scene='Lapatinib/Lapatinib/2' caption='Lapatinib, also known as Tykerb ([[3bbt]])'> | |||
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===Better Known as: Tykerb=== | |||
* Marketed By: GlaxoSmithKline | |||
* Major Indication: Breast [[Cancer]] | |||
* Drug Class: [[EGFR]] Inhibitor | |||
* Date of FDA Approval (Expiration): 2007 (2017) | |||
* 2009 Sales (Projected Peak): $150 Million ($4.5 Billion)<ref>http://money.cnn.com/2006/06/03/news/companies/glaxo_breastcancer/index.htm</ref> | |||
* Importance: It is one of the newest treatments for cancer. Complaints over the high cost ($22,000) for a treatment course which only prolongs survival in breast cancer patients by less than 2 months. It is particularly effective against HER2-positive breast [[cancer]]. | |||
* See [[Pharmaceutical Drugs]] for more information about other drugs and disorders | |||
===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='Lapatinib/Egfr/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 significant conformational shift, revealing an additional binding site capable of binding and activating downstream signaling proteins.<ref>PMID:6090945</ref><ref>PMID:16729045</ref> Erlotinib inhibits the EGFR tyrosine kinase by <scene name='Lapatinib/Egfbb/1'>binding to the ATP-binding site</scene> located within the kinase domain. Residues Met 774, Leu 825, Val 707, Thr 835, Asp 836, Phe 837, Thr 771, Lys 726, Ala 724, & Leu 769 tightly bind the inhibitor in place. 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:15374980</ref> | |||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
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{{:Tyrosine Kinase Inhibitor Pharmacokinetics}} | |||
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</StructureSection> | |||
===References=== | |||
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