Structure-guided discovery of adenosine triphosphate-competitive casein kinase 2 inhibitors

Casein kinase 2 (CK2) is a ubiquitous, highly pleiotropic serine-threonine kinase. CK2 has been identified as a potential drug target for the treatment of cancer and related disorders. Several adenosine triphosphate-competitive CK2 inhibitors have been identified and have progressed at different levels of clinical trials. This review presents details of CK2 protein, structural insights into adenosine triphosphate binding pocket, current clinical trial candidates and their analogues. Further, it includes the emerging structure-based drug design approaches, chemistry, structure-activity relationship and biological screening of potent and selective CK2 inhibitors. The authors tabulated the details of CK2 co-crystal structures because these co-crystal structures facilitated the structure-guided discovery of CK2 inhibitors. The narrow hinge pocket compared with related kinases provides useful insights into the discovery of CK2 inhibitors.

Automated summary

Casein kinase 2 (CK2) is a widely present serine-threonine kinase with diverse functions. It has emerged as a potential drug target for cancer and related disorders. This review provides a comprehensive overview of CK2 protein, its binding pocket, current clinical trial candidates, and structure-guided drug design approaches for CK2 inhibitors. The authors also discuss the importance of CK2 co-crystal structures in facilitating inhibitor discovery.