Pharmacophore approaches in protein kinase inhibitors design

Our review, dedicated to the analysis of pharmacophore models for protein kinase inhibitors design has been published in World Journal of Pharmacology.

Abstract: Protein kinases constitute a superfamily of therapeutic targets for a number of human and animal diseases that include more than 500 members accordingly to sequencing data of the human genome. The well characterized nature of protein kinases makes them excellent targets for drug development. Pharmacophore approaches have become one of the major tools in the area of drug discovery. Application of pharmacophore modeling approaches allows reducing of expensive overall cost associated with drug development project. Pharmacophore models are important functional groups of atoms in the proper spatial position for interaction with target protein. Various ligand-based and structure-based methods have been developed for pharmacophore model generation. Despite the successes in pharmacophore model generation these approaches have not reached their full capacity in application for drug discovery. In the following review, we summarize the published data on pharmacophore models for inhibitors of tyrosine protein kinases (EGFR, HER2, VEGFR, JAK2, JAK3, Syk, ZAP-70, Tie2) and inhibitors of serine/threonine kinases (Clk, Dyrk, Chk1, IKK2, CDK1, CDK2, PLK, JNK3, GSK3, mTOR, p38 MAPK, PKB). Here, we have described the achievements of pharmacophore modeling for protein kinase inhibitors, which provide key points for further application of generated pharmacophore hypotheses in virtual screening, de novo design and lead optimization.

• Pharmacophore approaches in protein kinase inhibitors design. Starosyla SA, Volynets GP, Bdzhola VG, Golub AG, Yarmoluk SM. World J. Pharmacol. 2014, 3(4):162-173.