Kinase Inhibitors and Computer-Aided Drug Design Methods

The development of protein kinase inhibitors (PKI) is a prominent research field in medicinal chemistry. The pivotal role of protein kinases in all stages of cell life has made this one of the most sought-after targets for the treatment of a growing array of diseases. This protein family, however, offers many challenges, specially related to selectivity. From this perspective, both its function plurality and conserved structure are at many times a double-edged sword. Advances in computer-aided drug development (CADD) tools have immensely influenced protein kinase research, playing a determinant role in different hallmarks in PKI history. Nowadays, it is the utmost important tool for inhibitor design. In this chapter, we introduce the basics of kinase function, structure, and inhibitor design. We discuss its relevance as a drug target and introduce case studies where computer-aided design methods have helped identify or optimize new compounds.