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    ZM 323881 HCl
    ZM 323881 HCl

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0523
    CAS #: 193000-39-4Purity ≥98%

    Description: ZM323881 HCl (ZM-323881 Hydrochloride) is a novel, potent and selective tyrosine kinase VEGFR2 inhibitor with potential antitumor activity. It inhibits human vascular endothelial growth factor receptor 2 (VEGFR2) with an IC50 of<2 nM, and shows little/ no activity against other kinases such as VEGFR1, PDGFRβ, FGFR1, EGFR and ErbB2. ZM323881. ZM323881 inhibits VEGF-A-induced endothelial cell proliferation (IC50 = 8 nM) and VEGF-R2 tyrosine phosphorylation in vitro. ZM323881 (10 nM) blocks VEGF-induced Rac1 activation at 30 min in HUVECs.

    References: Microcirculation. 2002 Dec;9(6):513-22; Biochem Biophys Res Commun. 2006 Apr 14;342(3):851-8.

    Related CAS #: 193001-14-8; 324077-30-7 (free base); 193000-39-4 (HCl)    

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    olecular Weight (MW)411.86
    CAS No.193000-39-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 10 mg/mL (24.3 mM)
    Water: <1 mg/mL
    Ethanol:<1 mg/mL
    Solubility (In vivo)1% CMC Na: 20 mg/mL

    Synonym: ZM323881; ZM 323881; ZM323881 hydrochloride; ZM-323881; ZM323881 HCl; ZM 323881 hydrochloride; ZM-323881 hydrochloride; ZM 323881 HCl; ZM-323881 HCl; 

    Chemical Name: 5-((7-Benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methylphenol hydrochloride


    InChi Code: InChI=1S/C22H18FN3O2.ClH/c1-14-9-18(23)20(11-21(14)27)26-22-17-8-7-16(10-19(17)24-13-25-22)28-12-15-5-3-2-4-6-15;/h2-11,13,27H,12H2,1H3,(H,24,25,26);1H

    SMILES Code: OC1=CC(NC2=C3C=CC(OCC4=CC=CC=C4)=CC3=NC=N2)=C(F)C=C1C.[H]Cl

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    In Vitro

    In vitro activity: ZM323881 inhibits VEGF-A, EGF and bFEF induced HUVEC cell proliferation with IC50 of 8 nM, 1.9 μM and 1.6 μM, respectively. ZM323881 (10 nM) abolishes VEGF-A-mediated increases in vascular permeability in perfused mesenteric microvessels in male leopard. ZM323881 (10 nM) blocks the increase in intensity of the VEGF-R2 band in the lung of male leopard frogs. ZM323881 (1 μM) blocks activation of extracellular regulated-kinase, p38, Akt, and endothelial nitric oxide synthetase (eNOS) by VEGF, but did not inhibit p38 activation by the VEGFR-1-specific ligand, placental growth factor (PIGF) in human aortic endothelial cells (HAECs). ZM323881 (1 μM) also perturbes VEGF-induced membrane extension, cell migration, and tube formation by HAECs. ZM323881 (1 μM) reverses VEGF-stimulated phosphorylation of CrkII and its Src homology 2 (SH2)-binding protein p130Cas, which are known to play a pivotal role in regulating endothelial cell migration. ZM323881 (10 nM) completely blocks VEGF-induced VEGF promoter activity in SCC-9 cells. ZM323881 (10 nM) blocks VEGF stimulated Hif-1α protein accumulation in SCC-9 cells. ZM323881 (10 nM) blocks VEGF-induced Rac1 activation at 30 min in HUVECs. ZM323881 (10 nM) prevents Vav2 tyrosine phosphorylation in response to VEGF in HUVECs. ZM323881 (< 1 μM) inhibits VEGF stimulated neural stem cell proliferation in a dose-dependent manner. ZM323881 (< 1 μM) inhibits neural stem cell proliferation in a dose-dependent manner even when no exogenous VEGF is added.

    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

    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

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    Microcirculation. 2002 Dec;9(6):513-22; Biochem Biophys Res Commun. 2006 Apr 14;342(3):851-8.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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