Casein kinase 2 is a ubiquitous kinase protein emerging as a target for the treatment of cancer. Several active CK2 inhibitors have been developed in the last few years; most of them have ATP-competitive type of inhibition. Indenoindoles present a class of natural and synthetic compounds; many of them have different bioactivity. Here we report on the development of a ligand-based pharmacophore on the basis of different active indenoindoles (training set), the pharmacophore model was challenged against small library of indenoindoles (test set), the study was performed using MOE software. Our model demonstrates good performance in the test set, 85% of the medium or high inhibitory activity compounds were identified, while only 17% of the low or no inhibitory activity compounds were misclassified. Several structures were suggested as possible active CK2 inhibitors by using this model as a base for search in the ZINC database among them was bikaverin which was then further studied.