Motesanib, Diphosphate

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; C_max = 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.

Cell permeable: yes

Primary Target
VEGFR

Reversible: yes

Target IC₅₀: 2 nM, 3 nM, 6 nM, 6 nM, 8 nM for VEGFR1, VEGFR2, Flk-1, VEGFR3, and KIT respecitively

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Wang, Y., et al. 2014. Biochem. Pharmacol.90, 367.

Benjamin, R., et al. 2011. Cancer Chemother. Pharmacol.68, 69.

Li, C., et al. 2009. Drug Metab. Dispos.37, 1378.

Sherman, S., et al. 2008. N. Engl. J. Med.359, 31.

Polverino, A., et al. 2006. Cancer Res.66, 8715.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)