How druggable is protein kinase CK2?

Abstract

CK2 is a pleiotropic, ubiquitous, and constitutively active protein kinase (PK), with both cytosolic and nuclear localization in most mammalian cells. The holoenzyme is generally composed of two catalytic (alpha and/or alpha') and two regulatory (beta) subunits, but the free alpha/alpha' subunits are catalytically active by themselves and can be present in cells under some circumstances. CK2 catalyzes the phosphorylation of more than 300 substrates characterized by multiple acidic residues surrounding the phosphor-acceptor amino acid, and, consequently, it plays a key role in several physiological and pathological processes. But how can one kinase orchestrate all these tasks faithfully? How is it possible that one kinase can, despite all pleiotropic characteristics of PKs in general, be involved in so many different biochemical events? Is CK2 a druggable target? Several questions are still to be clearly answered, and this review is an occasion for a fruitful discussion.

CK2¿, over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells

“…Further studies are warranted to show evidence for patients who may potentially benefit from CK2 inhibitors. CK2 inhibitors have not been extensively developed as therapeutic agents, partly because the ATP-binding pocket of CK2 is not as druggable as some other protein kinases [44][45][46]. To date, only one small-molecule CK2 inhibitor has been entered to clinical trials as a potential anticancer drug [47].…”

Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser 16 to trigger its nuclear localization

“…3B). Several other cell-permeable CK2 inhibitors are available, but the majority of them are less selective than TDB and quinalizarin (39)(40)(41).…”

Urolithin as a Converging Scaffold Linking Ellagic acid and Coumarin Analogues: Design of Potent Protein Kinase CK2 Inhibitors

“…[1,2] Its catalytic subunits (a and/or a') are constitutively active either with or without the regulatory b-subunits, which appear to play a role in targeting and substrate recruiting, rather than controlling catalytic activity. Furthermore, constitutively active CK2 is ubiquitous, essential, and implicated in a wide variety of important cell functions.…”