Sunitinib

spinqualitylabelsall models Sunitinib, also known as Sutent, (3g0e) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Better Known as: Sutent

• Marketed By: Pfizer
  
• Major Indication: Renal Cell Carcinoma & Gastrointestinal Cancer
  
• Drug Class: Receptor Tyrosine Kinase (Including VEGFR & PDGFR) & KIT Cytokine Receptor Inhibitor
• Date of FDA Approval (Patent Expiration): 2006 (2020)
  
• 2009 Sales: $964 Million
• Importance: Currently among the most effective cancer treatments available. Sunitinib is the first treatment for renal cell carcinoma to demonstrate an overall survival of longer than two years. Has very impressive results with gastrointestinal stromal tumors. It was the first cancer drug to be approved simultaneously for two different indications. Controversial due to its high cost of $38,000 per year.
• See Pharmaceutical Drugs for more information about other drugs and disorders.

Mechanism of Action

Sunitinib inhibits cellular signaling by targeting several different receptor tyrosine kinases (RTKs) including receptors for platelet-derived growth factor (PDGFRs) and vascular endothelial growth factor receptors (VEGFR). PDGFR and VEGFR play crucial roles in both tumor angiogenesis and cellular proliferation. Inhibition of PDGFR and VEGFR results in reduced tumor vascularization and cancer cell death. Sunitinib is also an inhibitor of KIT, a cytokine receptor inhibitor. KIT binds to stem cell factor, upon which KIT dimerizes and transmit second messenger signals ultimately resulting in cell survival and proliferation. Mutations of the KIT gene are associated with most gastrointestinal stromal tumors.

Pharmacokinetics

Tyrosine Kinase Inhibitor Pharmacokinetics VEGFR & KIT Inhibitors EGFR Inhibitors BCR-Abl Inhibitor Parameter Sunitinib (Sutent) Sorafenib (Nexavar) Erlotinib (Tarceva) Gefitinib (Iressa) Lapatinib (Tykerb) Imatinib (Gleevec) Nilotinib (Tasigna) Dasatinib (Sprycel) Tmax (hr) 8 8.3 2.0 5.4 4 3.7 3.0 1.0 Cmax (ng/ml) 24.6 460 69.6 130 115 2070 411 124 Bioavailability (%) Variable 29-49 99 59 Variable 98 30 20 Protein Binding (%) 95 99 93 90 99 95 98 96 T1/2 (hr) 83 29 9.4 26.9 9.6 26.6 16.0 3.3 AUC (ng/ml/hr) 1921 11040 20577 3850 1429 4760 10052 461 Dosage (mg) 50 50 150 250 100 400 200 200 Metabolism Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) For Pharmacokinetic Data References, see: References