ZM323881_hydrochloride_DataSheet_MedChemExpress

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Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
ZZZM 323881 Hcl is a potent and selective VEGFR2 inhibitor with IC50 of <2 nM, almost no activity on VEGFR1, PDGFRβ, FGFR1, EGFR and ErbB2.
IC50 value: <2 nM [1]
Target: VEGFR2
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 [1]. M323881 (1μM) 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 [2]. 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 [3]. 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 [4].
PROTOCOL (Extracted from published papers and Only for reference)
Kinase assay (Binding assay) [1]
ZM323881 is incubated (20 minutes, room temperature) with enzyme in an HEPES (pH 7.5) buffered solution containing 10 mM MnCl2and 2 μM ATP, in 96–well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. IC50 data are interpolated by nonlinear regression (four–parameter logistic equation) using Microcal Origin software.
References:
[1]. Whittles CE, et al. ZM323881, a novel inhibitor of vascular endothelial growth factor–receptor–2 tyrosine kinase activity. Microcirculation, 2002, 9(6),513–522.
[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. Assay Drug Dev Technol, 2011, 9(2), 125–135.
[3]. Slomiany MG, et al. IGF–1 induced vascular endothelial growth factor secretion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun, 2006, 342(3), 851–858.
[4]. Garrett TA, et al. VEGF–induced Rac1 activation in endothelial cells is regulated by the guanine nucleotide exchange factor Vav2. Exp Cell Res, 2007,
Product Name:
ZM323881 (hydrochloride)Cat. No.:
HY-15467A CAS No.:
193000-39-4Molecular Formula:
C 22H 19ClFN 3O 2Molecular Weight:
411.86Target:
VEGFR Pathway:
Protein Tyrosine Kinase/RTK Solubility:
10 mM in DMSO
313(15), 3285–3297.
Caution: Product has not been fully validated for medical applications. For research use only.
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