1. Discovery and biological evaluation of potent dual ErbB-2/EGFR tyrosine kinase inhibitors: 6-thiazolylquinazolines
- Author
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Yu Guo, Sarva M. Tadepalli, G. Stuart Cockerill, Kathryn Smith, Edgar R. Wood, Barry R. Keith, David W. Rusnak, Robert J. Mullin, Micheal D. Gaul, Robert J. Griffin, Wilson B. Knight, Tona M. Gilmer, Karen Lackey, Stephen Barry Stevenage Guntrip, Karen Affleck, and Doris M. Murray
- Subjects
Receptor, ErbB-2 ,Clinical Biochemistry ,Transplantation, Heterologous ,Pharmaceutical Science ,Antineoplastic Agents ,Mice, Inbred Strains ,Biochemistry ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,Growth factor receptor ,ErbB ,In vivo ,Epidermal growth factor ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Enzyme Inhibitors ,skin and connective tissue diseases ,Molecular Biology ,biology ,Chemistry ,Organic Chemistry ,Neoplasms, Experimental ,In vitro ,Transplantation ,ErbB Receptors ,Enzyme inhibitor ,Cancer research ,biology.protein ,Quinazolines ,Molecular Medicine ,Female ,Signal transduction - 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.
- Published
- 2003