Ki8751

Catalog No.S1363 Batch:S136301

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Technical Data

Formula

C24H18F3N3O4

Molecular Weight 469.41 CAS No. 228559-41-9
Solubility (25°C)* In vitro DMSO 47 mg/mL (100.12 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
VEGFR2 [1] c-Kit [1] PDGFRα [1]
0.9 nM 40 nM 67 nM
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]

Protocol (from reference)

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

  • Method

    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.

Customer Product Validation

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]

Selleck's Ki8751 has been cited by 21 publications

Eph-ephrin signaling couples endothelial cell sorting and arterial specification [ Nat Commun, 2024, 15(1):2539] PubMed: 38570531
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.