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ZM-323881
Cat No.
CEI-0003
Description
ZM323881 inhibits VEGF-A-induced endothelial cell proliferation with IC50 of 8 nM.
CAS No.
193000-39-4
Molecular Weight
411.86
Purity
0.99
Storage
2 years -20centigrade Powder, 2 weeks 4centigrade in DMSO, 6 months -80centigrade in DMSO
Targets
VEGFR2
Molecular Formula
C22H18FN3O2.HCl
Chemical Name
4-fluoro-2-methyl-5-[(7-phenylmethoxyquinazolin-4-yl)amino]phenol
Solubility
DMSO 10 mg/mL, Water
In vitro
ZM323881 inhibits VEGF-A-induced endothelial cell proliferation with IC50 of 8 nM and VEGF-R2 tyrosine phosphorylation in vitro. VEGF-A-mediated increases in vascular permeability in perfused mesenteric microvessels in vivo can be reversibly abolished by ZM323881. ZM323881 inhibits activation of VEGFR-2, but not of VEGFR-1, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), or hepatocyte growth factor (HGF) receptor. SCC-9 cells express the VEGF receptors Flk-1 and neuropilin-1 (Np-1), with VEGF treatment increasing VEGF promoter activity and VEGF secretion that was attenuated by the Flk-1 tyrosine kinase inhibitor, ZM 323881. VEGF significantly increases VEGF promoter activity. Treatment of cells with the flk-1 tyrosine kinase inhibitor ZM323881 completely blocks this effect. VEGF can stimulate Hif-1alpha protein accumulation was blocked by treatment with ZM323881. The effects of ZM 323881 were specific based on its lack of effect on IGF-1 stimulated Hif-1alpha accumulation. ZM 323881 treatment alone reduces the basal expression of Hif-1alpha, consistent with the presence of a VEGF: VEGFR-2 autocrine loop in quiescent SCC-9 cells.
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