Exploring potential VEGF receptor 2 inhibitors: a molecular modeling and pharmacophore-based screening approach

The vascular endothelial growth factor (VEGF) receptor 2, a membrane tyrosine kinase receptor activated by VEGF-A, triggers endothelial cell proliferation, migration, survival, and angiogenesis. With the aim of identifying additional new ligands or acquiring novel information to craft potent drugs, the focus of this study was to point to this macromolecule as to a possible target for selective modulators or inhibitors. Using the Pharmit server, pharmacophore-based screening of about 450 million compounds was performed, yielding candidate ligands evaluated through molecular modeling tools such as molecular docking, molecular dynamics, and 3D quantitative structure–activity relationship analysis. The best complex, PubChem-143070699/VEGFR2, matched the proposed pharmacophore model and predicted nanomolar affinity. While experimental evidence remains mandatory to decipher the mechanisms underlying VEGFR2 inhibitors, the predicted structural insights gleaned from this research hold promise for advancing the development of increasingly potent and precisely targeted therapies for VEGFR-associated conditions, such as cancer and fibrosis-related diseases.