Binding‐Site Switch for Protein Kinase CK2 Inhibitors

• DOI: 10.1002/cmdc.202400868
• Publication Date: 2025-01-21T10:28:44Z
• Authors: Dylan Grenier; Muriel Gelin; Yinshan Yang; Angélique Mularoni; Jean‐François Gui...; Jean‐Guy Delcros; Isabelle Krimm
• Keywords: Casein kinase 2

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