High‐Throughput Screening for Kinase Inhibitors

Abstract

Following G protein‐coupled receptors (GPCRs), protein kinases have become the second most important class of targets for drug discovery over the last 20 years. While only four kinase inhibitors have reached the market to date (Fasudil for rho‐dependent kinase, Rapamycin for TOR, Gleevec for BCR‐Abl, and Iressa for EGFR), many more are already in clinical development. A historical overview of kinase inhibitors was recently published by Cohen.1 After the previous successes, protein kinases are now regarded as attractive, well‐drugable targets, and the analysis of the human genome has yielded 518 protein kinases.2 We can thus expect screening for protein kinase inhibitors to become even more important in the future. In this review we will focus on the early steps of drug discovery programs producing new lead compounds. We will guide the reader through efficient state‐of‐the‐art assay development and high‐throughput screening of large chemical libraries for protein kinase inhibitors.