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 lev...

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Bibliographic Details
Published in:Future medicinal chemistry 2023-06, Vol.15 (11), p.987-1014
Main Authors: Patel, Shivani, Vyas, Vivek K, Sharma, Manmohan, Ghate, Manjunath
Format: Article
Language:English
Subjects:
ATP-competitive CK2 inhibitors
cancer
casein kinase 2
structure-guided discovery
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Summary: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.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2023-0005