Knut Eis

Kinase Data Mining: Dealing with the Information (Over-)Flow

Since the discovery of the first protein kinase inhibitors in the 1980s, inhibition of kinase activity has become an increasingly important theme in pharmaceutical research. The successful introduction of kinase inhibitors as a new treatment paradigm in cancer has spurred vast scientific activities both in academia and in the pharmaceutical industry. The field of protein kinases and their inhibitors exhibits considerable complexity. The human kinome, the entirety of all protein kinases abundant in humans, encompasses no less than 500 different enzymes. Furthermore, as most of the known small-molecule inhibitors of protein kinases address the conserved ATPbinding site, many of them inhibit not just one but multiple kinases. This fact raises not only selectivity as a key issue in kinase research, but can also generate complex datasets in which inhibitor structures are linked to a panel of kinases. The broad scientific activity in the field has resulted in a sometimes perplexing wealth of publicly available information, making data mining and processing a substantial challenge. Searching for the concept “small molecule kinase inhibitor” on the Internet yielded over 50 000 hits. Since 2000, more than 6000 scientific papers and patents on kinase inhibitors have been published. The information is highly scattered amongst these sources and, for example, extracting and compiling biological activities against a certain set of kinase targets within a given molecular class may prove to be a truly daunting task. In addition, larger pharmaceutical research organizations running multiple kinase-inhibitor research projects generate large and complex sets of internal experimental data. The first part of this article contains a brief introduction to selected, publicly or commercially available information resources related to kinases and their inhibitors. Subsequently, we will describe eKID, a data warehouse set up at Schering AG to deal with the vast amount of external and internal data on smallmolecule kinase inhibitors.