Adenosine-anchored triphosphate subsite probing: distinguishing between HER-2 and HER-4 tyrosine protein kinases

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3587-92. doi: 10.1016/s0960-894x(03)00761-3.

Abstract

A strategy of full-site occupancy and stereospecific recognition in the triphosphate subsite was used to specifically inhibit two protein kinases HER-2 and HER-4 from the EGFR family. The SAR profiles of a panel of adenosine-anchored bicyclic heterocycles against HER-2 and HER-4 indicated that specificity can be derived for highly homologous protein kinases from stereospecific recognition in the triphosphate-subsite.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / chemistry*
  • Benzamides
  • Enzyme Inhibitors / chemistry
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / chemistry*
  • ErbB Receptors / metabolism
  • Imatinib Mesylate
  • Models, Molecular
  • Molecular Probes*
  • Phosphates / chemistry*
  • Piperazines / chemistry
  • Pyrimidines / chemistry
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / chemistry*
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-4
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Molecular Probes
  • Phosphates
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-4
  • Adenosine