A cell-permeable anthranilamide that acts as a potent VEGFR inhibitor (IC50=130, 23, and 18nM against VEGFR-1, -2, and -3, respectively; IC50=1.24nM against VEGF-induced human VEGFR-2 phosphorylation in CHO cells) by targeting the ATP-binding site of VEGFR in its inactive "DFG-out" conformation and effectively suppresses tumor growths (50 to 100mg/kg; p.o.) via its anti-angiogenesis activity in mice and rats in vivo, while inhibiting c-kit, CSF-1R/c-Fms, PDGFR-b, and c-Abl only at higher concentrations (IC50=236, 380, 640, and 2820nM, respectively). AAL933 and two other VEGFR inhibitors, KRN633 and SU5416, are also shown to inhibit hypoxia-induced HIF-1a expression (by <90% at 30uM) and transcription activation. Unlike KRN633 and SU5416, AAL933 prevents only hypoxia-induced Erk, but not Akt, phosphorylation in HeLa cells.
Molecular Formula:C₂₀H₁₆F₃N₃O
Molecular Weight:371.4
Solubility:DMSO (100mg/ml)
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.
