Research Area · Protein Kinase CK2

1,3-Thiazole-5-carboxylic Acid Derivatives

A virtual-screening-derived heterocyclic scaffold for the development of ligand-efficient CK2 inhibitors.

1,3-thiazole-5-carboxylate inhibitor bound within the ATP-binding pocket of protein kinase CK2

Virtual screening identified novel protein kinase CK2 inhibitors among 1,3-thiazole-5-carboxylic acid derivatives. The most active compound, 2-(3-fluorophenyl)-4-methyl-1,3-thiazole, inhibited CK2 with an IC50 value of 0.4 μM. Ligand-efficiency values for the investigated derivatives ranged from 0.45 to 0.56 kcal mol−1 per non-hydrogen atom. Given that 0.3 is generally considered the lower threshold for ligand efficiency, the identified CK2 inhibitors represent promising candidates for lead optimization. A binding mode for this compound class within the ATP-binding site of protein kinase CK2 was proposed (Figure 1).

Chemical structure and proposed binding mode of a 1,3-thiazole derivative within the ATP-binding site of protein kinase CK2
Figure 1. Complex of 2-(3-fluorophenyl)-4-methyl-1,3-thiazole with the ATP-binding site of protein kinase CK2. Hydrogen bonds are shown as dashed lines.

Publication

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