Biochem/physiol Actions
Reversible: yes
Primary TargetVEGFR
Target IC50: 2 nM, 3 nM, 6 nM, 6 nM, 8 nM for VEGFR1, VEGFR2, Flk-1, VEGFR3, and KIT respecitively
Cell permeable: yes
General description
A cell-permeable, bioavailable nicotinamide derivative that acts as a highly potent, ATP-competitive multi-kinase inhibitor (IC50 = 2, 3, 6, 8 nM for VEGFR1, VEGFR2, VEGFR3, and Kit, respectively). Also inhibits the activity of PDGFR and RET kinases, albeit at higher concentrations (IC50 = 84 and 39 nM, respectively). Does not affect the activities of EGFR, Src, and p38 kinases (IC50 >3 µM) and 47 other protein kinases. Inhibits VEGF-induced (IC50 = 10 nM), but not bFGF-induced (IC50 >3 µM) proliferation of HUVECs. Also shown to diminish VEGF-induced angiogenesis in a rat corneal model (ED50 = 2.1 mg/kg, b.i.d; p.o.) and suppresses the growth of A431 human epidermoid xenografts in mice (10 to 100 mg/kg, b.i.d). Displays desirable pharmacokinetic properties (t = 6.7 h; Cmax = 787 ng/ml).Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
A cell-permeable, bioavailable nicotinamide derivative that acts as a highly potent, ATP-competitive multi-kinase inhibitor (IC50 = 2, 3, 6, 8 nM for VEGFR1, VEGFR2, VEGFR3, and Kit, respectively). Also inhibits the activity of PDGFR and RET kinases, albeit at higher concentrations (IC50 = 84 and 39 nM, respectively). Does not affect the activities of EGFR, Src, and p38 kinases (IC50 >3 µM) and 47 other protein kinases. Inhibits VEGF-induced (IC50 = 10 nM), but not bFGF-induced (IC50 >3 µM) proliferation of HUVECs. Also shown to diminish VEGF-induced angiogenesis in a rat corneal model (ED50 = 2.1 mg/kg, b.i.d; p.o.) and suppresses the growth of A431 human epidermoid xenografts in mice (10 to 100 mg/kg, b.i.d). Displays desirable pharmacokinetic properties (t = 6.7 h; Cmax = 787 ng/ml).
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Other Notes
Wang, Y., et al. 2014. Biochem. Pharmacol.90, 367.r>Benjamin, R., et al. 2011. Cancer Chemother. Pharmacol.68, 69.r>Li, C., et al. 2009. Drug Metab. Dispos.37, 1378.r>Sherman, S., et al. 2008. N. Engl. J. Med.359, 31.r>Polverino, A., et al. 2006. Cancer Res.66, 8715.
Packaging
Packaged under inert gas
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Warning
Toxicity: Standard Handling (A)
This product has met the following criteria to qualify for the following awards: