Structure-based discovery of small molecules targeting different surfaces of protein-kinase CK2.

Protein kinase CK2 is an unfavorable pronostic marker in several cancers and has consequently emerged as a relevant therapeutic target. Several classes of ATP-competitive inhibitors have been identified, showing variable effectiveness. The molecular architecture of this multisubunit enzyme could offer alternative strategies to develop small molecule inhibitors targeting different surfaces of the kinase. Polyoxometalates were identified as original CK2 inhibitors targeting key structural elements located outside the active site. In addition, the CK2 subunit interface represents an exosite distinct from the catalytic cavity that can be targeted by peptides or small molecules to achieve functional effects. Copyright 2009 Elsevier B.V. All rights reserved.