1,3-thiazole-5-carboxylic acid derivatives

Novel CK2 inhibitors among 1,3-thiazole-4-carboxylic acid derivatives have been identified using virtual screening. The most active compound 2-(3-Fluoro-phenyl)-4-methyl-1,3-thiazole inhibits 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. 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. The binding mode for compounds in this class with ATP-binding site of CK2 has been proposed (Fig. 1). 

Figure 1. The binding mode of compound 2-(3-Fluoro-phenyl)-4-methyl-1,3-thiazole in the CK2 active site. Hydrogen bonds are shown by the dotted lines.

• Identification of 1,3-thiazole-5-carboxylic acid derivatives as inhibitors of protein kinase CK2. Protopopov MV, Volynets GP, Starosyla SA, Vdovin VS, Lukashov SS, Bilokin YV, Bdzhola VG, Yarmoluk SM. Curr Enzyme Inhib. 2018, 14(2): 152-159.