nrf2 inducers eq an effective inducer of are regulated enzymes is docked into the ivr structural model without any preset preference between cavities c288 and c297 eq is docked into cavity c297 automatically using software gold probably because of the fact that the cavity around c288 is shallow next the keap1 ivr eq complex is employed to virtually screen 90 000 compounds extracted from the nci 3d chemical database ncl us for putative nrf2 inducers the chemical structures and the predicted binding modes for each of the 50 top score compounds are visually inspected a multiple cycle screening strategy is used in the first cycle chemical samples for 23 top score compounds are obtained of the 23 compounds seven hits are identified using are driven luciferase assays in the second cycle the ncl 3d database for the analogues of the initial hits by a ligand based approach using the tanimoto index with a cutoff of 0 9 is screened chemical samples of 17 analogues are obtained of the hits from the first cycle and then they are subjected to cell based assays the two cycles of screenings identify 9 novel nrf2 inducers scheme 1 below are driven luciferase assays and western blot analyses of the top score compounds have identified novel nrf2 inducers the 23 top score molecules from the first round of virtual screening are initially tested in the cell based are driven luciferase assay specifically hepg2 cell line are transfected with are driven pgl3 luciferase vector and then exposed to individual test compounds at 10.