The Current Status of Drug Discovery Against the Human Kinome

Protein kinases are important targets in drug discovery programs aimed at treating many devastating diseases, including cancer, autoimmune disorders, diabetes, and neurological disorders. Most “classical” drug discovery efforts employ rational drug design methods based upon structural information to identify compounds targeting the enzyme catalytic domain. Novel information on kinase biology is opening up other approaches in the design of selective inhibitors that may provide more subtle modulation of these drug discovery targets. The identification of such modulators requires adoption of a new generation of high-throughput screening techniques. These approaches will allow measurement of conformational changes in kinases, as well as protein–protein interactions via assessment of functional responses such as cellular translocation. Therefore a range of novel techniques, together with the understanding that numerous “orphan” kinases will provide targets for therapeutics, suggests that a new era of kinase th...