Structure-Based Pharmacophore Modeling from Multicomplex: a Comprehensive Pharmacophore Generation of Protein Kinase CK2 and Virtual Screening Based on it for Novel Inhibitors.

Protein kinase CK2, a member of the serine/threonine kinase family, is an attractive therapeutic target for anticancer combination therapy. A multiple structure-based modeling approach complemented with shape components was taken to build a reliable pharmacophore model for ATP-competitive CK2 inhibitors. The final model consisted of one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), two hydrophobic (HY) features, several excluded volumes and shape constraints. In the validation study, this model yielded an enrichment factor of 10.22 and performed fairly well in distinguishing active compounds. SPECS database was searched based on this query and sixteen compounds were retained after multiple filtrations for biological test. 4 compounds with IC50 values less than 10 µM were disclosed, providing 2 new chemical scaffolds as CK2 inhibitors. It is expected that the information provided here is helpful for discovering more potential CK2 inhibitors.