high metabolic activity which results inincreased cellular levels of such toxic metabolites. Therefore, tumour cells respond to this increase by increasing theactivity of the detoxifying glyoxalase system which makes it a viable target for the development of anticancer drugs. This work represents the first study that aims to find none-glutathione-based inhibitors of the glyoxalase-II enzyme aspotential anticancer drugs based on computer aided drug design. In this study, a customized 3D structure-basedpharmacophore model was generated which is a hybrid of three complementary 3D pharmacophores. Since glyoxalase-II is a binuclear zinc metalloenzyme, a customized Zn-binding pharmacophoric feature was added to the generatedpharmacophore to aid the search for selective glyoxalase-II inhibitors through virtual screening of small-moleculesdatabases. Retrieved hits were extensively filtered then docked into the binding site of the enzyme. In order tomaximize the chances of finding potential inhibitors of glyoxalase-II, docked hits were rescored using different scoringfunctions and consensually scored. Ten of the top ranked hits were selected as potential glyoxalase-II inhibitors