Semaxanib

IdentifiersCAS NumberPubChem CIDIUPHAR/BPSChemSpiderUNIIChEBIChEMBLChemical and physical dataFormulaC₁₅H₁₄N₂OMolar mass238.290 g·mol⁻¹3D model (JSmol) ^NY (what is this?)  (verify)

Semaxanib (INN,^[1] codenamed SU5416) is a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic. It is an experimental stage drug, not licensed for use on human patients outside clinical trials. Semaxanib is a potent and selective synthetic inhibitor of the Flk-1/KDR vascular endothelial growth factor (VEGF) receptor tyrosine kinase. It targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential.^{[citation needed]}

Research

In February 2002, Pharmacia, the then-parent of Sugen, prematurely ended phase III clinical trials of semaxinib in the treatment of advanced colorectal cancer due to discouraging results.^[2] Other studies, at earlier phases, have since been conducted.^[3][4] However, due to the prospect of next-generation tyrosine kinase inhibitors and the inefficacy of semaxanib in clinic trials, further development of the drug has been discontinued.^[5] A related compound, SU11248 (sunitinib), was further developed by Sugen and subsequently by Pfizer, and received FDA approval for treatment of renal carcinoma in January 2006.^[6]

When combined with chronic exposure to hypoxia, SU5416 induces severe pulmonary hypertension in mice and rats. This property has been exploited to develop a series of useful, though controversial, rodent models of pulmonary arterial hypertension, the first and best characterized being the Sugen/Hypoxia (SuHx) mouse model.^[7][8]

References