Docking study yields four novel inhibitors of the protooncogene Pim-1 kinase

J Med Chem. 2008 Mar 27;51(6):1972-5. doi: 10.1021/jm701248t. Epub 2008 Feb 22.

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.

MeSH terms

  • Computer Simulation*
  • Drug Design*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Ligands
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-pim-1