The Discovery of Novel Protein Kinase Inhibitors by Using Fragment-Based High-Throughput X-ray Crystallography

This article describes the application of a high-throughput X-ray crystallographic fragment-based screening methodology to identify low-molecular-weight leads for structure-based optimisation into protein kinase inhibitors. The identification of two novel p38α MAP kinase inhibitors (with IC50=65 and 150 nM) starting from low-molecular-weight fragments is described.