Receptor-based pharmacophore modeling, molecular docking, synthesis and biological evaluation of novel VEGFR-2, FGFR-1, and BRAF multi-kinase inhibitors.

ABSTRACT: A receptor-based pharmacophore model describing the binding features required for the multi-kinase inhibition of the target kinases (VEGFR-2, FGFR-1, and BRAF) were constructed and validated. It showed a good overall quality in discriminating between the active and the inactive in a compiled test set compounds with F1 score of 0.502 and Mathew's correlation coefficient of 0.513. It described the ligand binding to the hinge region Cys or Ala, the glutamate residue of the Glu-Lys αC helix conserved pair, the DFG motif Asp at the activation loop, and the allosteric back pocket next to the ATP binding site. Moreover, excluded volumes were used to define the steric extent of the binding sites. The application of the developed pharmacophore model in virtual screening of an in-house scaffold data

SUBMITTER: Abdel-Mohsen HT 

PROVIDER: S-EPMC10893631 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature