Trastuzumab

Better Known as: Herceptin Marketed By: Genentech Major Indication: Breast Cancer Drug Class: Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitor Date of FDA Approval (Discontinued): 1998 (2015) 2008 Sales: $4.75 Billion Importance: It is a very effective treatment against HER2-positive metastatic breast cancer compared to other cancer therapies. Controversial due to its cost of nearly $100,000 per year. Is often pointed to as an example of the benefits of personalized medicine in which a patent's genetic profile is used to optimize their medication regimen. See Pharmaceutical Drugs for more information about other drugs and disorders Mechanism of Action Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in approximately 30% of breast cancers. Upon receiving a mitogenic signal, HER2, located in the cell membrane, dimerizes and transfers signals to receptors within the cell. This activates different pathways including the PI3K pathway and MAPK pathway, promoting cellular survival and replication. Trastuzumab is a humanized monoclonal antibody of the extracellular segment of the HER2 receptor. It has been suggested that Trastuzumab binding disrupts receptor dimerization, preventing the errant signal from being transfered. This ultimately causes cells to arrest druing the G1 phase of the cell cycle, halting cellular proliferation. between the Trastuzumab antibody Fab and HER2 involves residues Arg 58, Arg 50, Tyr 33, Tyr 100, & Gly 99 on the heavy chain Fab, Thr 94, His 91, Tyr 92, Tyr 32, & Tyr 53 on the light chain Fab, and Glu 558, Gln 561, Asp 560, Phe 573, Lys 569, Pro 572, Pro 571, Lys 593, Cys 601, Cys 604 & Gln 602 on the HER2 polypeptide. Pharmacokinetics EGFR Inhibitor Pharmacokinetics Parameter Trastuzumab Tmax (hr) 1.7 Cmax (ng/ml) 203000 Bioavailability (%) 54 T1/2 (days) 27 AUC (ug/ml/hr) 45036 Clearance (L/h) .009 Dosage (mg) 250 Metabolism Unknown

spinqualitylabelsall models Tastuzumab, better known as Herceptin, (3be1) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image