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.
Micheal D Gaul  1 ,  Yu Guo ,  Karen Affleck ,  G Stuart Cockerill ,  Tona M Gilmer ,  Robert J Griffin ,  Stephen Guntrip ,  Barry R Keith ,  Wilson B Knight ,  Robert J Mullin ,  Doris M Murray ,  David W Rusnak ,  Kathryn Smith ,  Sarva Tadepalli ,  Edgar R Wood ,  Karen Lackey
Affiliations
  • 1. GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
PMID: 12639547 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.

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