A new series of potent oxindole inhibitors of CDK2

Bioorg Med Chem Lett. 2004 Feb 23;14(4):913-7. doi: 10.1016/j.bmcl.2003.12.009.


A novel series of oxindole-type inhibitors of CDK2 that have heteroatom substituted alkynyl moieties at their C-4 position is described. These novel 4-alkynyl-substituted inhibitors have superior potency relative to their parent compound in free enzyme and in cell based assays. The crystal structure of CDK2 in complex with one of these analogues was determined and gives insight to their increased potency. The biochemical evaluation of a representative derivative is also described.

MeSH terms

  • CDC2-CDC28 Kinases / antagonists & inhibitors*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 2
  • DNA / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Paclitaxel / pharmacology
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Indoles
  • DNA
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Paclitaxel