Recent Advances in the Discovery of CK2 Allosteric Inhibitors: From Traditional Screening to Structure-Based Design

Molecules

Dada Wang¹  Chunqiong Li²  Xiaolan Chen³  Yu Chen³  Na Zhang³ 

[1] Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China;;Beijing Key Laboratory of Environmental &Jiangsu Agri-animal Husbandry Vocational College, Taizhou 225300, China;

关键词: protein kinase (ck2);    allosteric site;    allosteric inhibitors;    traditional screening;   

DOI  :  10.3390/molecules25040870

来源: DOAJ

【 摘 要 】

Protein kinase (CK2) has emerged as an attractive cancer therapeutic target and recent efforts have been made to develop its inhibitors. However, the development of selective inhibitors remains challenging because of the highly conserved ATP-binding pocket (orthosteric site) of kinase family. As an alternative strategy, allosteric inhibitors, by targeting the much more diversified allosteric site relative to the conserved ATP-binding site, achieve better pharmacological advantages than orthosteric inhibitors. Traditional serendipitous screening and structure-based design are robust tools for the discovery of CK2 allosteric inhibitors. In this review, we summarize the recent advances in the identification of CK2 allosteric inhibitors. Firstly, we briefly present the CK2 allosteric sites. Then, the allosteric inhibitors targeting the well-elucidated allosteric sites (α/β interface, αD pocket and interface between the Glycine-rich loop and αC-helix) are highlighted in the discovery process and possible binding modes with the allosteric sites are described. This study is expected to provide valuable clues for the design of CK2 allosteric inhibitors.

【 授权许可】

Unknown