CK2 Inhibitors

We have identified seven classes of ATP-competitive small-molecular inhibitors of protein kinase CK2 using computer-based rational design approach.

Protein kinase CK2 (formerly known as casein kinase 2 or II) is a ubiquitous, highly conserved serine/threonine kinase, and recent studies have shown that it can also phosphorylate tyrosine residues. CK2 phosphorylates > 300 substrates involved in DNA replication, gene transcription, signal transduction, and cell growth and apoptosis.

CK2 expression and activity are up-regulated in blood tumors, including multiple myeloma and leukemia, and in solid tumors, including kidney, mammary gland, lung, prostate, and head and neck cancers. While the precise roles of CK2 in tumorigenesis are still not completely understood, anti-apoptosis functions of CK2 through the regulation of tumor suppressor and oncogene activity have been suggested.

Also, recently have been reported that CK2 is a target protein for glomerulonephritis (GN) therapy, supported by experiments showing that administration of an antisense oligodeoxynucleotide against CK2 or low-molecular weight CK2-specific inhibitors effectively prevented progression of the renal disease in a rat model of GN. It has also been revealed that some viruses use CK2 to phosphorylate functionally critical proteins encoded in their genome; consequently, the important role of CK2 in the development of viral infections has been shown. In addition, new data provide evidence of the key role of CK2 in mediation of growth factor effects in normal and pathological angiogenesis, CK2 inhibitors significantly decrease oxygen-induced retinal neovascularization in mice and could be successfully used for therapy of proliferative retinopathies, for example, in diabetes.

Taking into account these facts, nowadays CK2 is considered as druggable protein kinase target and could be used for the development of antitumor, antiviral and anti-inflammatory drugs. Therefore the goal of our laboratory research is focused on the development new potent and selective inhibitors of protein kinase CK2.