The Virtual Target Screening Of N-benzyl-4-methyl-1,2-Phenylenediamine Derivatives

The95-99lead compounds from Pro.Tan’s laboratory were confirmed to be efficacious in inhibiting FAK in the vitro experiments.Using PDTD as the target protein database and with the help of Autodock and Discovery,we took the targets screening program.We found VEGFR,Ras,PKC,ERK and p38may be possible targets for the95-99molecules.Then with the analysis of the lead compounds further docking to Ras and p38,we found95-99molecules strongly binding to the GDP pocket of Ras.95-99molecules form H-bonds with the binding site which make them a stable combining status.The residues of the H-bonds involve VAL29,GLU31and ASN116,which may be the key residues.95-99molecules also can be binding to the ATP pocket of p38and form H-bonds with the residues in the pocket.And the binding energy is lower than SB203580,which reveals the great potential of inhibit ability of the lead compound.The related residues in the ATP pocket involve GLU71,ASP168and GLY170.GLU71and ASP168has been reported as the key residues of p38inhibition.This series of lead compound can both be combined with Ras and p38,which means they have potential of being multi-target drugs.And we also discovered the possible mechanism of FAK inhibition from the analysis of the docking conformations...