Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors

Virtual screening was performed to determine potent vascular endothelial growth factor receptor (VEGFR)-2 kinase inhibitors. A database of approximately 820,000 commercial compounds was used for screening, and 100 compounds were chosen as candidate VEGFR-2 inhibitors through pharmacophore modeling and docking studies. These 100 compounds were purchased to test their biological activities: 10 compounds were found to inhibit the enzyme, with IC50 values ranging from 10 to 1 μM. Compound 1, which has a triazinoindole ring, inhibited the enzymatic activity of VEGFR-2, with an IC50 value of about 1.6 μM, making it the most potent inhibitor of this enzyme. The triazinoindole derivative may therefore serve as the starting point in the design of new VEGFR-2 kinase inhibitors.

Graphical abstractUsing a combination of pharmacophore Modeling and virtual screening, a novel VEGFR-2 inhibitor has been identified.Figure optionsDownload full-size imageDownload as PowerPoint slide