General description

An orally bioavailable amino-triazole compound that is shown to bind to the inactive conformations of both PDGFRβ and Raf kinases (allosteric, Type II inh), and acts as a potent inhibitor of Flt3, Kit, PDGFRα and PDGFRβ (K_d = 52, 170, 300 and 520 nM, respectively) with selectivity over B-Raf, p38α, FGFR2 and VEGFR2 (K_d >10 µM) in a multi-kinase panel. Completely blocks the phosphorylations of MEK-1/2 S217/S221, ERK-1/2 T202/Y204 in FGF-stimulated HUVECs, PDGFRβ in PDGF-BB-stimulated VSMCs, ERK-1/2 T202/Y204 in 1205Lu-B Raf V600E cells, and C-Raf S338 at 10 µM. Reduces FGF-induced angiogenesis in mouse Matrigel model (50 mg/kg, i.p., bid) and selectively induces apoptosis in the endothelium; further, suppresses orthotopic renal cell carcinoma growth in mice (100 mg/kg, p.o., qd).

Legal Information

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

Other Notes

Murphy, E.A., et al. 2010. Proc. Natl. Acad. Sci. USA107, 4299.

Packaging

Packaged under inert gas

10 mg in Glass bottle

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)