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Ki8751

产品号 S1363 公司名称 Selleck Chemicals
CAS号 228559-41-9 公司网站 http://www.selleckchem.com
分子式 C24H18F3N3O4 电 话 (877) 796-6397
分子量 469.4126296 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 72637

产品价格信息

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产品别名

标题
Ki8751
IUPAC标准名
1-(2,4-difluorophenyl)-3-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-2-fluorophenyl}urea
IUPAC传统名
1-(2,4-difluorophenyl)-3-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-2-fluorophenyl}urea

产品登记号

CAS号 228559-41-9

产品性质

作用靶点 VEGFR
作用靶点 c-Kit
作用靶点 PDGFR
作用靶点 FGFR
成盐信息 Free Base
溶解度 DMSO
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Cancer
Biological Activity
Description Ki8751 is a potent and selective inhibitor of VEGFR2 with IC50 of 0.9 nM.
Targets VEGFR2 PDGFRα c-Kit FGFR-2
IC50 0.9 nM 67 nM 40 nM 170 nM [1]
In Vitro Ki8751 potently and selectively inhibits VEGFR2 with IC50 of 0.9 nM. Ki8751 also inhibits PDGFRα, c-Kit, and FGFR-2, with much higher IC50 values (40 nM–170 nM). Except for these several kinases, Ki8751 doesn’t disturb other kinases, including HGFR, EGFR, and InsulinR, even at 10 μM. [1]In human umbilical vein endothelial cells (HUVECs), Ki8751 (1 nM–100 nM) effectively decreases VEGF-stimulated cell proliferation and vasculature permeability. [2]In metastatic colorectal cancer (CRC) cells MIP, RKO, SW620, and SW480, but not in HCT116, Ki8751 (10 nM) increases cellular senescence. [3]
In Vivo In nude mice bearing human tumor xenografts of GL07, St-4, LC6, DLD-1, and A375 cells, Ki8751 (20 mg/kg) inhibits tumor growth. In nude rat xenograft models of LC-6 cells, Ki8751 (5 mg/kg) completely inhibits tumor growth without affecting body weight. [1]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Cellular Kinase Assays NIH3T3 cells prepared by transfection of human KDR. The cells are cultured in a collagen type I coated 96-well plate in an amount of 1.5 × 104 per well. The medium is then replaced by a DMEM medium containing 0.1% FCS. Ki8751 diluted in DMSO is added to each well and cultured. rhVEGF is added to a final concentration of 100 ng/mL, and the stimulation of cells is carried out at 37 °C. The cells are washed with PBS (pH 7.4), 50 μL of a solubilization buffer (20 mM HEPES (pH 7.4), 150 mM NaCl, 0.2% Triton X-100, 10% glycerol, 5 mM Na3VO4, 5 mM disodium ethylenediamine tetraacetate, and 2 mM Na4P2O7) is then added and a cell extract is prepared. Separately, PBS (50 μL, pH 7.4) containing 5 μg/mL of antiphosphotyrosine antibody (PY20) is added to a microplate for ELISA. After washing of the plate, 300 μL of a blocking solution is added. The cell extract is transferred to the plate. An anti-VEGFR2 antibody and a peroxidase-labeled anti-rabbit Ig antibody are added. Next, a chromophoric substrate for peroxidase is added, and the absorbance at 450 nm is measured with microplate reader. The VEGFR2 phosphorylation activity for each well is determined by presuming the absorbance with the addition of VEGF and without the addition of the test sample to be 100% VEGFR2 phosphorylation activity and VEGF to be 0% VEGFR2 phosphorylation activity. The concentration of the inhibition (%) of VEGFR2 Phosphorylation is determined for each case, and IC50 value is calculated.
Cell Assay [1]
Cell Lines HUVECs
Concentrations 1 nM–100 nM
Incubation Time 1 hour
Methods To evaluate the inhibition of VEGF-Stimulated HUVEC proliferation by Ki8751, HUVECs are plated at a density of 4000 cells/200 μL/well in a type I collagen pre-coated 96-well plates. After 24 hours, the cells are incubated for 1 hour with Ki8751 and then stimulated with 20 ng/mL rhVEGF. The cultures are incubated at 37 °C for 72 hours, then pulsed with 1 μCi/well [3H]thymidine and re-incubated for 14 hours. Cells are assayed for the incorporation of tritium using a beta counter.
Animal Study [1]
Animal Models Nude mice bearing human tumor xenografts of GL07, St-4, LC6, DLD-1, and A375 cells
Formulation
Doses 20 mg/kg
Administration Administered orally once a day for 9 consecutive days
References
[1] Kubo K, et al. J Med Chem, 2005, 48(5), 1359-1366.
[2] Tamura D, et al. Cancer Sci, 2010, 101(6), 1403-1408.
[3] Hasan MR, et al. Int J Cancer, 2011, 129(9), 2115–2123.