Abstract
Vascular endothelial growth factor (VEGF) is a key stimulant of angiogenesis, which is the process of generating new capillary blood vessels. Inhibition of the vascular endothelial growth factor receptor (VEGFR) kinase is known to result in blockage of angiogenesis. A pharmacophore was developed based on the binding of ATP to the hinge region of the kinase domain of VEGFR and a database search of 18,000 compounds was conducted. Selected hits were assessed for their ability to limit the induction of web-like network of capillary tubes by the human umbilical vascular endothelial cells. Two compounds (1 and 4) showed good inhibitory ability to prevent sprouting and closed polygon formation of the tubular networks, promising them to be lead compounds. Compound 4 showed 60% inhibition at 0.05 μM.
| Original language | English |
|---|---|
| Pages (from-to) | 4125-4129 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 15 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 15 2005 |
Funding
Work at NSU was supported in part by the grant from The Florida Board of Education, State of Florida, provided through the Center of Excellence for Biomedical and Marine Biotechnology at FAU.
ASJC Scopus Subject Areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Keywords
- Angiogenesis
- Drug discovery
- Kinase inhibitor
- VEGFR
Disciplines
- Biochemistry
- Medical Biochemistry
- Molecular Biology
- Medical Molecular Biology
- Organic Chemistry
- Pharmacy and Pharmaceutical Sciences