Résumé
The serine/threonine protein kinase CK2, a tetramer composed of a regulatory dimer (CK2β2) bound to two catalytic subunits CK2α, is a well‐established therapeutic target for various pathologies, including cancer and viral infections. Several types of CK2 inhibitors have been developed, including inhibitors that bind to the catalytic ATP‐site, bivalent inhibitors that occupy both the CK2α ATP‐site and the αD pocket, and inhibitors that target the CK2α/CK2β interface. Interestingly, the bivalent inhibitor AB668 shares a similar chemical structure with the interface inhibitor CCH507. In this study, we designed analogs of CCH507 using structure‐based and fragment‐based approaches. The ability of these analogs to bind the CK2α/CK2β interface was evaluated using biolayer interferometry and fluorescence anisotropy‐based assays. Their potency to inhibit CK2 kinase activity was determined using the bioluminescent ADP‐Glo assay. These experiments allowed us to investigate which chemical modifications prevent the binding of the compounds at the CK2α/CK2β interface. Seven out of sixteen compounds conserved the ability to bind at the protein‐protein interface, among which three compounds exhibited better interface inhibition compared to CCH507.