Toward a Pharmacophore for Kinase Frequent Hitters
Alex M. Aronov, Mark A. Murcko · Journal of Medicinal Chemistry · 2004
Small molecule protein kinase inhibitors are widely employed as biological reagents and as leads in the design of drugs for a variety of diseases. One of the hardest challenges in kinase inhibitor design is achieving target selectivity. By utilizing X-ray structural information for four promiscuous inhibitors, we propose a five-point pharmacophore for kinase frequent hitters, demonstrate its ability to discriminate between frequent hitters and selective ligands, and suggest a strategy for selective inhibitor design.