228559-41-9

Basic information

• Product Name: Ki8751
• Synonyms: Ki8751 hydrate;N-(2,4-Difluorophenyl)-N'-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]-2-fluorophenyl]urea;1-(2,4-difluorophenyl)-3-(4-(6,7-diMethoxyquinolin-4-yloxy)-2-fluorophenyl)urea;N-(2,4-Difluorophenyl)-N'-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]-2-fluorophenyl]urea KI8751;Ki8751, >=98%;VEGFR2 Kinase Inhibitor VI, Ki8751;Ki8751;1-(2,4-Difluoro-phenyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-urea hydrate
• CAS NO: 228559-41-9
• Molecular Formula: C24H18F3N3O4
• Molecular Weight: 469.417
• Product Categories: Inhibitors;KI8751 ada@tuskwei.com sky;18031153937@189.cn
• Mol File: 228559-41-9.mol
• Article Data: 1

Chemical Properties

• Melting Point: 239℃
• Boiling Point: 497.1 °C at 760 mmHg
• Flash Point: 254.4 °C
• Appearance: /
• Density: 1.429
• Vapor Pressure: 5.12E-10mmHg at 25°C
• Refractive Index: 1.656
• Storage Temp.: −20°C
• Solubility: Soluble in DMSO (15 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Ki8751(CAS DataBase Reference)
• NIST Chemistry Reference: Ki8751(228559-41-9)
• EPA Substance Registry System: Ki8751(228559-41-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-38
• Safety Statements: 37
• Hazardous Substances Data: 228559-41-9(Hazardous Substances Data)

Usage

Description

KI8751 is a cell-permeable quinolyloxyphenyl-urea compound that acts as a potent and selective inhibitor of VEGFR2, PDGFRα, and c-Kit. It is characterized by its high potency with IC50 values of 0.9 nM for VEGFR2, 67 nM for PDGFRα, and 40 nM for c-Kit. KI8751 is effective in blocking VEGF-dependent cell proliferation and tumor growth in various in vitro and in vivo assays.

Uses

Used in Oncology:
KI8751 is used as an inhibitor of VEGFR2-tyrosine kinase for inhibiting the proliferation of human umbilical vein endothelial cells and tumor growth. It is particularly effective in suppressing the growth of various types of cancer cells by targeting the VEGFR2 pathway, which plays a crucial role in angiogenesis and tumor progression.
Used in Anticancer Drug Development:
KI8751 is used as a potent and selective inhibitor of VEGFR2, PDGFRα, and c-Kit in the development of novel anticancer drugs. Its high potency and selectivity make it a valuable compound for designing targeted therapies against various types of cancer.
Used in Anti-Influenza Applications:
KI8751 is used as an anti-influenza agent, displaying activity against both Influenza A and B viruses. It works by disrupting virus entry in a PDGFRα/GM3-dependent manner, offering a potential therapeutic approach for the treatment of influenza infections.
Used in Pharmaceutical Research:
KI8751 is used as a research tool in the study of various receptor and non-receptor kinases, as well as in the investigation of VEGF-dependent cell proliferation and tumor growth mechanisms. Its high potency and selectivity make it a valuable compound for understanding the roles of these targets in cellular processes and disease progression.

Biological Activity

Potent, selective inhibitor of VEGFR-2 tyrosine kinase (IC 50 = 0.9 nM). Displays some inhibitory activity towards c-Kit, PDGFR α and FGFR-2 (IC 50 values range from 40 to 170 nM) but is highly selective over other receptor tyrosine kinases (IC 50 > 10000 nM for FGFR-2, EGFR and HGFR). Inhibits VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) and inhibits tumor growth in vivo ; antiangiogenic.

References

Kubo et al. (2005), Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N’{4-(4-quinolyloxy)phenyl}ureas; J. Med. Chem. 48 1359 Vrijens et al. (2019), Influenza virus entry via the GM3 ganglioside-mediated platelet-derived growth factor receptor b signaling pathway; J. Gen. Virol. 100 583

InChI:InChI=1/C24H18F3N3O4/c1-32-22-11-15-20(12-23(22)33-2)28-8-7-21(15)34-14-4-6-19(17(27)10-14)30-24(31)29-18-5-3-13(25)9-16(18)26/h3-12H,1-2H3,(H2,29,30,31)

Upstream product

• 59025-55-7 2,4-diflurophenylisocyanate 
• 228559-74-8 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline 
• 228559-87-3 4-(3-fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline 
• 127285-54-5 1,4-dihydro-6,7-dimethoxy-4-oxoquinoline 
• 4101-30-8 2-amino-4,5-dimethoxyacetophenone 
• 35654-56-9 6,7-dimethoxy-4-chloroquinoline 

Relevant articles and documents

Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: Synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N′-{4-(4-quinolyloxy)phenyl}ureas

N-Phenyl-N′-{4-(4-quinolyloxy)phenyl}ureas were found to be a novel class of potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase through synthetic modifications of a lead compound and structure-activity relationship studies. A representative compound 6ab, termed Ki8751, inhibited VEGFR-2 phosphorylation at an IC50 value of 0.90 nM, and also inhibited the PDGFR family members such as PDGFRα and c-Kit at 67 nM and 40 nM, respectively. However, 6ab did not have any inhibitory activity against other kinases such as EGFR, HGFR, InsulinR and others even at 10000 nM. 6ab suppressed the growth of the VEGF-stimulated human umbilical vein endothelial cell (HUVEC) on a nanomolar level. 6ab showed significant antitumor activity against five human tumor xenografts such as GL07 (glioma), St-4 (stomach carcinoma), LC6 (lung carcinoma), DLD-1 (colon carcinoma) and A375 (melanoma) in nude mice and also showed complete tumor growth inhibition with the LC-6 xenograft in nude rats following oral administration once a day for 14 days at 5 mg/kg without any body weight loss.