ZM 323881 HCl

Names

[ CAS No. ]:
193000-39-4

[ Name ]:
ZM 323881 HCl

[Synonym ]:
ZM 323881 HCl
5-{[7-(Benzyloxy)quinazolin-4-yl]amino}-4-fluoro-2-methylphenol hydrochloride (1:1)
Phenol, 4-fluoro-2-methyl-5-[[7-(phenylmethoxy)-4-quinazolinyl]amino]-, hydrochloride (1:1)
5-{[7-(Benzyloxy)-4-quinazolinyl]amino}-4-fluoro-2-methylphenol hydrochloride (1:1)
ZM 323881 hydrochloride
5-[(7-Benzyloxyquinazolin-4-yl)amino]-4-fluoro-2-methylphenol hydrochloride

Biological Activity

[Description]:

ZM323881 hydrochloride is a potent and selective VEGFR2 inhibitor with an IC50 of less than 2 nM.

[Related Catalog]:

Research Areas >> Cancer

[Target]

VEGFR2:2 nM (IC50)

[In Vitro]

ZM323881 is an anilinoquinazoline that potently inhibits VEGFR2 (KDR) tyrosine kinase activity anddemonstrates excellent selectivity versus other receptor tyrosine kinases, including PDGFRβ, FGFR1, EGFR and erbB2 (IC50>50 μM). ZM323881 inhibits VEGF-A-induced endothelial cell proliferation(IC50=8 nM) and VEGFR2 tyrosine phosphorylation[1]. 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. In HAECs, ZM323881 completely inhibits VEGF-induced ERK phosphorylation at 1 μM[2]

[Kinase Assay]

Compounds (ZM323881) are incubated (20 minutes, room temperature) with enzyme in an N-2-hydroxyethylpiperazine-N'-2-ethanesulphonate (HEPES) (pH 7.5) buffered solution containing 10 mM MnCl2 and 2 μM ATP, in96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. Phosphorylated tyrosine is then detected bysequential incubation with mouse IgG anti-phosphotyrosine antibody a horseradish peroxidase(HRP)-linked sheep anti-mouse Ig antibody and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid). IC50 data are interpolated by nonlin-ear regression[1].

[Cell Assay]

HUVEC cells isolated from umbilical cords are plated (at passage 2–8) in 96-wellplates (1000 cells/well) and dosed with ZM323881±VEGF-A (3 ng/mL), EGF (3 ng/mL), or basicfibroblast growth factor (bFGF, 0.3 ng/mL). The cultures are then incubated for 4 days. On day 4, the cultures are pulsed with 1 μCi/well of 3H-thymidine and reincubated for 4 hours. The cells are then harvested and assayed for the incorporation of tritium by using a beta-counter. IC50 data are interpolated[1].

[References]

[1]. Whittles CE, et al. ZM323881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity. Microcirculation. 2002 Dec;9(6):513-22.

[2]. Endo A, et al. Selective inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) identifies a central role for VEGFR-2 in human aortic endothelial cell responses to VEGF. J Recept Signal Transduct Res. 2003;23(2-3):239-54.

[Related Small Molecules]

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₂H₁₉ClFN₃O₂

[ Molecular Weight ]:
411.857

[ Exact Mass ]:
411.114990

[ PSA ]:
67.27000

[ LogP ]:
5.98050

[ Storage condition ]:
-20℃

ZM 323881 HCl

Names

Biological Activity

Chemical & Physical Properties

Related Compounds