Structural biology in drug design: selective protein kinase inhibitors

Protein kinases have a fundamental role in signal transduction pathways, and aberrant kinase activity has been observed in many diseases. In recent years, kinase inhibition has become a major area for therapeutic intervention and a variety of kinase inhibitor pharmacophores has been described. This review illustrates some of the efforts and results in the field of structure-based design of protein kinase inhibitors. The methods and results discussed here illustrate the power of structure-based design in lead discovery, for example via virtual screening and in guiding the optimization of the pharmacological properties of these molecules.