Docking Study Yields Four Novel Inhibitors of the Protooncogene Pim-1 Kinase

• DOI: 10.1021/jm701248t
• Publication Date: 2008-02-22T06:00:35Z
• Authors: Albert C. Pierce; Marc Jacobs; Cameron Stuver-Moody
• Keywords: Models, Molecular; 0301 basic medicine; Structure-Activity Relationship; 03 medical and health sciences; Molecular Structure; Proto-Oncogene Proteins c-pim-1; Drug Design; Humans; Computer Simulation; Stereoisomerism; Ligands; Protein Kinase Inhibitors

To supplement the hits from a high throughput screen, docking was performed against Pim-1 kinase. Glide docking was augmented with a filter to require traditional or aromatic CH..O hydrogen bonds to the kinase hinge. Four diverse actives, of 96 molecules assayed, had K(i) values between 0.091 and 4.5 microM. This gives a 14-fold enrichment over the earlier HTS run, and the two crystal structures solved confirmed the binding modes predicted by docking.