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

Abstract

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.