Structural insights into the conformational selectivity of STI-571 and related kinase inhibitors

Curr Opin Drug Discov Devel. 2004 Sep;7(5):639-48.


STI-571 (Gleevec) is a highly successful cancer drug due to its activity as an inhibitor of the Abelson cytoplasmic tyrosine kinase (Abl), which is constitutively active in a majority of patients with chronic myelogenous leukemia. STI-571 also inhibits two type III receptor tyrosine kinases, c-Kit and platelet-derived growth factor receptor, and functions by targeting inactive conformations of these kinases. This review focuses on recent developments in X-ray co-crystal structure analyses of STI-571 bound to Abl and the c-Kit receptor tyrosine kinase domain, and also three other relevant kinase inhibitor co-crystal structures. The similar structural features of these inactive kinases suggest they will be useful for the successful drug discovery and development of specific and targeted gene-based cancer drugs.

Publication types

  • Review

MeSH terms

  • Benzamides
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Imatinib Mesylate
  • Molecular Conformation*
  • Molecular Structure
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use


  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate