1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1133-6. doi: 10.1016/s0960-894x(03)00034-9.

Abstract

1H-Pyrazolo[3,4-b]pyridine 3 (SQ-67563) has been shown to be a potent, selective inhibitor of CDK1/CDK2 in vitro. In cells 3 acts as a cytotoxic agent with the ability to block cell cycle progression and/or induce apoptosis. The solid state structure of 3 bound to CDK2 shows 3 resides coincident with the ATP purine binding site and forms important H-bonding interactions with Leu83 on the protein backbone.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Biological Assay
  • CDC2 Protein Kinase / antagonists & inhibitors
  • CDC2-CDC28 Kinases*
  • Cell Cycle / drug effects
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Conformation
  • Ovarian Neoplasms / drug therapy
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology*
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • 1H-pyrazolo(3,4-b)pyridine
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyrazoles
  • Pyridines
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases