Design of Novel Ras Farnesyltransferase Inhibitors Based on Virtual Screening and Docking Studies

초록

Inhibition of the protein-modifying enzyme farnesyltransferase is considered as a major emerging strategy in cancer therapy because of the involvement of farnesylated proteins in oncogensis. We studied the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. FlexX docking of inhibitors confirmed reasonable fit of the molecule into the peptide binding site of farnesyltransferase. We also performed a virtual screening with LeadQuest chemical library databases to identify novel inhibitors of farnesyltransferase. Finally, detail docking studies were performed using these compounds which showed high scoring from the virtual screening experiment.