Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI)

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4355-9. doi: 10.1016/j.bmcl.2003.09.028.


We describe the discovery, using shape-based virtual screening, of a potent, ATP site-directed inhibitor of the TbetaRI kinase, an important and novel drug target for fibrosis and cancer. The first detailed report of a TbetaRI kinase small molecule co-complex confirms the predicted binding interactions of our small molecule inhibitor, which stabilizes the inactive kinase conformation. Our results validate shape-based screening as a powerful tool to discover useful leads against a new drug target.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Drug Evaluation, Preclinical / methods
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Kinetics
  • Molecular Conformation
  • Phosphorylation
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta
  • User-Computer Interface


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Receptors, Transforming Growth Factor beta
  • Adenosine Triphosphate
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I