Sunitinib

Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases (RTKs).Like RCC, GIST does not generally respond to standard chemotherapy or radiation. Imatinib was the first cancer agent proven effective for metastatic GIST and represented a major development in the treatment of this rare but challenging disease. However, approximately 20% of patients do not respond to imatinib (early or primary resistance), and among those who do respond initially, 50% develop secondary imatinib resistance and disease progression within two years. Prior to sunitinib, patients had no therapeutic option once they became resistant to imatinib.The drug was discovered at SUGEN, a biotechnology company which pioneered protein kinase inhibitors. It was the third in a series of compounds including SU5416 and SU6668. The concept was of an ATP mimic that would compete with ATP for binding to the catalytic site of receptor tyrosine kinases. This concept led to the invention of many small-molecule tyrosine kinase inhibitors, including Gleevec, Sutent, Tarceva and many others.Sunitinib adverse events are considered somewhat manageable and the incidence of serious adverse events low.Epigallocatechin-3-gallate, a major constituent of green tea, may reduce the bioavailability of sunitinib when they are taken together.Sunitinib is marketed by Pfizer as Sutent, and is subject to patents and market exclusivity as a new chemical entity until February 15, 2021. Sutent has been cited in financial news as a potential revenue source to replace royalties lost from Lipitor following the expiration of the latter drug's patent expiration in November 2011. Sutent is one of the most expensive drugs widely marketed. Doctors and editorials have criticized the high cost for a drug that does not cure cancer, but only prolongs life.