Discovery and biological evaluation of potent dual ErbB-2/EGFR tyrosine kinase inhibitors: 6-thiazolylquinazolines

Bioorg Med Chem Lett. 2003 Feb 24;13(4):637-40. doi: 10.1016/s0960-894x(02)01047-8.

Abstract

We have identified a novel class of 6-thiazolylquinazolines as potent and selective inhibitors of both ErbB-2 and EGFR tyrosine kinase activity, with IC(50) values in the nanomolar range. These compounds inhibited the growth of both EGFR (HN5) and ErbB-2 (BT474) over-expressing human tumor cell lines in vitro. Using xenograft models of the same cell lines, we found that the compounds given orally inhibited in vivo tumor growth significantly compared with control animals.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mice, Inbred Strains
  • Neoplasms, Experimental / drug therapy
  • Quinazolines / chemical synthesis*
  • Quinazolines / pharmacokinetics*
  • Quinazolines / pharmacology
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Quinazolines
  • ErbB Receptors
  • Receptor, ErbB-2