Abstract

Background: Serine/threonine protein kinase CK2 is involved in the regulation of a number of cellular functions such as cell growth, proliferation, differentiation and apoptosis. Increased activity of CK2 is associated with the development of different types of cancer, inflammatory response, pain and virus infections. Therefore, protein kinase CK2 is an attractive molecular target for the development of small-molecular inhibitors which can be important compounds for pharmaceutical application.

Objective: The main aim of this research is to identify novel chemical class of CK2 inhibitors with good lead-like properties.

Methods: In order to find novel CK2 inhibitors, virtual screening experiments were performed using Autodock software. Best-scored compounds were tested in vitro using P32 radioactive kinase assay.

Results: Small-molecular inhibitors of protein kinase CK2 were identified among the derivatives of 1,3-thiazole-5-carboxylic acid. The most active compound inhibited CK2 with IC50 value of 0.4 μM. Ligand efficiency for studied derivatives of 1,3-thiazole-5-carboxylic acid was in the range from 0.45 to 0.56 kcal/mol/non-hydrogen atom.

Conclusion: Considering the fact that the lower limit for ligand efficiency parameter is 0.3, the identified CK2 inhibitors among the derivatives of 1,3-thiazole-5-carboxylic acid are excellent candidates for further lead optimization.

Keywords: 1, 3-thiazole-5-carboxylic acid, inhibitor, kinase assay, ligand efficiency, molecular docking, protein kinase СК2.

Graphical Abstract