Prediction of specificity-determining residues for small-molecule kinase inhibitors

Background: Designing small-molecule kinase inhibitors with desirable selectivity profiles is a major challenge in drug discovery. A high-throughput screen for inhibitors of a given kinase will typically yield many compounds that inhibit more than one kinase. A series of chemical modifications are usually required before a compound exhibits an acceptable selectivity profile. Rationalizing the selectivity profile for a small-molecule inhibitor in terms of the specificitydetermining kinase residues for that molecule can be an important step toward the goal of developing selective kinase inhibitors. Results: Here we describe S-Filter, a method that combines sequence and structural information to predict specificity-determining residues for a small molecule and its kinase selectivity profile. Analysis was performed on seven selective kinase inhibitors where a structural basis for selectivity is known. S-Filter correctly predicts specificity determinants that were described by independent ...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Daniel R. Caffrey, Elizabeth A. Lunney, Deborah J. Moshinsky
• Keywords: BMCBI 2008, Kinase, Kinase Inhibitors, Selectivity Profiles