Evaluation of in vitro activity and SAR study of the novel hetarylamino-3-aryl-1H-indazole derivatives as inhibitors of protein kinase CK2

Aim. To identify novel protein kinase CK2 inhibitors among the 5-hetarylamino-1H-indazoles. Methods. Biochemical testing was carried out with the aid of γ- 32 P ATP in vitro kinase assay. Molecular docking via the Autodock 4.2.6 program package was executed, rescoring of docking results was performed using DrugScore scoring function. Results. Among the 17 studied 5-amino-3-arylindazole derivatives 11 inhibitors of protein kinase CK2 with IC 50 in nanomolar range were identified. The most active compound has IC 50 = 2 nM. SAR study and addi-tional molecular modeling of these compounds allowed us to select prospective substituents for construction of novel compounds with improved activity and physicochemical properties. Conclusions. As a result of this work 11 nanomolar protein kinase CK2 inhibitors were de-veloped and the binding modes of these compounds with the ATP-acceptor site were proposed using molecular docking methods. The physicochemical properties and SAR of substituents of studied compounds were analyzed and 6 novel compounds were designed for further development as protein kinase CK2 inhibitors. Summarizing, 5-heterylamino-1H-indazoles are a good basis for further CK2 inhibitors development.