Doing more than just the structure—structural genomics in kinase drug discovery

Structural genomics (SG) has significantly increased the number of novel protein structures of targets with medical relevance. In the protein kinase area, SG has contributed >50% of all novel kinases structures during the past three years and determined more than 30 novel catalytic domain structures. Many of the released structures are inhibitor complexes and a number of them have identified new inhibitor binding modes and scaffolds. In addition, generated reagents, assays, and inhibitor screening data provide a diversity of chemogenomic data that can be utilized for early drug development. Here we discuss the currently available structural data for the kinase family considering novel structures as well as inhibitor complexes. Our analysis revealed that the structural coverage of many kinases families is still rather poor, and inhibitor complexes with diverse inhibitors are only available for a few kinases. However, we anticipate that with the current rate of structure determination and high throughput technologies developed by SG programs these gaps will be closed soon. In addition, the generated reagents will put SG initiatives in a unique position providing data beyond protein structure determination by identifying chemical probes, determining their binding modes and target specificity.