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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C24H18F3N3O4 |
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分子量 | 469.41 | CAS No. | 228559-41-9 | ||||
Solubility (25°C)* | 体外 | DMSO | 53 mg/mL (112.9 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Ki8751 is a potent and selective inhibitor of VEGFR2 with IC50 of 0.9 nM, >40-fold selective for VEGFR2 than c-Kit, PDGFRα and FGFR-2, little activity to EGFR, HGFR and InsR. |
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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] |
キナーゼアッセイ | Cellular Kinase Assays | |
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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. | ||
細胞アッセイ | 細胞株 | HUVECs |
濃度 | 1 nM–100 nM | |
反応時間 | 1 hour | |
実験の流れ | 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. |
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動物実験 | 動物モデル | Nude mice bearing human tumor xenografts of GL07, St-4, LC6, DLD-1, and A375 cells |
投薬量 | 20 mg/kg | |
投与方法 | Administered orally once a day for 9 consecutive days |
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Data from [Mol Cell Proteomics, 2012, 11, 745-57]
Data from [Data independently produced by , , Cancer Lett, 2017, 385:12-20]
Data from [Data independently produced by , , PLoS One, 2016, 11(9):e0161332]
Paeonol Promotes Reendothelialization After Vascular Injury Through Activation of c-Myc/VEGFR2 Signaling Pathway [ Drug Des Devel Ther, 2023, 17:1567-1582] | PubMed: 37249931 |
Anlotinib exerts potent antileukemic activities in Ph chromosome negative and positive B-cell acute lymphoblastic leukemia via perturbation of PI3K/AKT/mTOR pathway [ Transl Oncol, 2022, 25:101516] | PubMed: 35985203 |
Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death [ Front Oncol, 2021, 11:650052] | PubMed: 34094940 |
Network Pharmacology Reveals the Mechanism of Activity of Tongqiao Huoxue Decoction Extract Against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia-Reperfusion Injury [ Front Pharmacol, 2020, 11:572624] | PubMed: 33519437 |
Network Pharmacology Reveals the Mechanism of Activity of Tongqiao Huoxue Decoction Extract Against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia-Reperfusion Injury [ Front Pharmacol, 2020, 11:572624] | PubMed: 33519437 |
miR-221-3p Regulates VEGFR2 Expression in High-Risk Prostate Cancer and Represents an Escape Mechanism from Sunitinib In Vitro. [ J Clin Med, 2020, 9(3)] | PubMed: 32131507 |
Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors. [ Cell Rep, 2019, 28(9):2331-2344] | PubMed: 31461650 |
Roxadustat promotes angiogenesis through HIF-1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats. [ Wound Repair Regen, 2019, 27(4):324-334] | PubMed: 30817065 |
Secretion-mediated STAT3 activation promotes self-renewal of glioma stem-like cells during hypoxia [ Oncogene, 2018, 37(8):1107-1118] | PubMed: 29155422 |
Decreased abundance of TRESK two-pore domain potassium channels in sensory neurons underlies the pain associated with bone metastasis. [ Sci Signal, 2018, 11(552)] | PubMed: 30327410 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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