Discovery of novel CK2 leads by cross-docking based virtual screening.

Protein kinase CK2, a serine/threonine kinase, is an attractive therapeutic target for many diseases. Here we described an application of cross-docking based drug design to discover novel and potent CK2 leads. Glide SP was chosen as the most suitable docking approach by comparing four docking protocols through native-docking. Then twenty-four CK2 crystal structures were compared by recovering known active ligands from a decoy database to select the optimal ensemble of CK2 structures, 2PVN, 2ZJW, 3AMY, 3FL5 and 3KXH were severed as the assemble, which were used in the virtual screening of compiled SPECS database for small molecules inhibiting CK2. Seven compounds were selected and purchased to test the biological activity. Compound g (AQ-390/42425635) showed the best inhibition rate and the lowest IC50, which can be used as a lead for our subsequent optimization.