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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.

CK2 scheme

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.

4-aminothieno[2,3-d]pyrimidines

CK2_nhtpNovel CK2 inhibitors among 4-aminothieno[2,3-d]pyrimidines have been identified. The most active compounds obtained in the course of the research are...

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2-aminopyrimidinones and their 6-aza-analogs

ck2_img_new2In order to find the new potent CK2 inhibitors 60 derivatives of 2-aminopyrimidinones and their 6-aza-substituted analogs were synthesized and tested in vitro. Among them, the most...

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2-phenylisothiazolidin-3-one-1,1-dioxides

ck2_im_new2We have synthesized 40 new 2-phenylisothiazolidin-3-one-1,1-dioxide derivatives. The optimization based on biological screening data and molecular modeling resulted in a 10-fold increase...

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4'-hydroxyflavones

ck2 img6The novel synthetic flavone inhibitors (4'-hydroxyflavones) were identified with receptor-based virtual screening of combinatorial library containing 150,000 organic compounds. Followed...

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4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones (TID)

Figure 1. The binding mode of TID46 in the CK2 active site. Hydrogen bonds are shown by the dotted lines.The novel potent and specific CK2 inhibitors - 4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones (TID) was identified by high-throughput docking of OTAVA compound collection containing...

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3-carboxy-4(1H)-quinolones

Figure 1. The binding mode of Quinolone 9 in the CK2 active site. Hydrogen bonds are shown by the dotted lines.This CK2 inhibitors were revealed and evaluated to be a CK2 inhibitors after receptor-based virtual screening (docking) of around 70,000 compounds, coming from the Otava compound library...

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3-hydroxy-4'-carboxyflavone derivatives (FLC)

ck2 img7With the aim to identify new CK2 inhibitors virtual screening of 150,000 small organic compounds has been performed. As a result, were have found and tested in vitro 13...

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(thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids (TTP)

Figure 1. The binding mode of TTP22 in the CK2 active site. Hydrogen bonds are shown by the dotted lines.To study CK2 inhibitory activity of substituted (thieno[2,3-d] pyrimidin-4-ylthio)carboxylic acids, 28 compounds of this class were synthesized and tested in vitro. The most active...

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Other kinase inhibitors research:

ASK1 Inhibitors
Evaluation of 2-Thioxo-thiazolidin-4-ones Derivatives as Inhibitors of ASK1 Image
In order to discover novel ASK1 inhibitors we have performed screening program,...



 

CK2 Inhibitors
(thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids (TTP) Image
To study CK2 inhibitory activity of substituted (thieno[2,3-d]...



 

FGFR1 Inhibitors
Oxindoles Image
Oxindoles are known class of inhibitors of RTK, including FGFR1. We perform...



 

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