Structure-guided discovery of adenosine triphosphate-competitive casein kinase 2 inhibitors
Shivani Patel1, Vivek K Vyas1, Manmohan Sharma1
1Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India.
Abstract:
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.
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