An oxazine that appears to mimic the pyranosidic moiety of heparin sulfate, and is shown to interact directly with several growth factors and cytokines including VEGF, TNF-a and heparin-binding-EGF in a surface plasmon resonance assay. At concentrations of 10-80uM, this compound dose-dependently inhibits the proliferation of VEGF-expressing LM8G7 cells (IC50=13uM), and TNF-a-expressing OVSAHO cells (IC50=19uM). At 195uM, a 99% reduction in cell growth is observed in HB-EGF-expressing SKOV-3 cultures. This compound inhibits heparanase-mediated degradation of heparin sulfate in LM8G7 cells (IC50=65uM and 104-206uM, in an enzymatic and a cell based assay, respectively). At 0.5-5uM, it markedly prevents the migration and invasion of the same culture, in a dose-dependent manner. In addition, it completely suppresses liver metastatic nodules of osteosarcoma mice injected with LM8G7 cells at 0.5mg/kg without any signs of toxicity in vivo, and demonstrates a synergistic anti-tumor effect when dosed with heparin.
Formula:C22H25F2NO2
Molecular Weight:373.4
Solubility:DMSO
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
