Discovery of dual kinase inhibitors targeting VEGFR2 and FAK: structure-based pharmacophore modeling, virtual screening, and molecular docking studies.

ABSTRACT: VEGFR2 and FAK signaling pathways are interconnected and have synergistic effects on tumor angiogenesis, growth, and metastasis. Thus, instead of the conventional targeting of each of these proteins individually with a specific inhibitor, the present work aimed to discover novel dual inhibitors targeting both VEGFR2 and FAK exploiting their association. To this end, receptor-based pharmacophore modeling technique was opted to generate 3D pharmacophore models for VEGFR2 and FAK type II kinase inhibitors. The generated pharmacophore models were validated by assessing their ability to discriminate between active and decoy compounds in a pre-compiled test set of VEGFR2 and FAK active compounds and decoys. ZINCPharmer web tool was then used to screen the ZINC database purchasable subset using t

SUBMITTER: Fouad MA 

PROVIDER: S-EPMC10863211 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature