New Protein Kinase CK2 Inhibitors: Jumping out of the Catalytic Box

Protein kinases are central components of signal transduction cascades often dysregulated in cancer, and they represent some of the most promising drug targets. However, the target selectivity is a major concern because most described kinase inhibitors target the highly conserved ATP-binding pocket. Recently, new classes of inhibitors that do not compete with ATP and exhibit different mechanisms of action have been described. Overexpression of protein kinase CK2 is an unfavorable prognostic marker in several cancers. Consequently, CK2 has 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 inhibit CK2 functions, and this review illustrates these emerging possibilities.