title: Discovery and biological evaluation of potent dual ErbB-2/EGFR tyrosine kinase inhibitors: 6-thiazolylquinazolines.
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.
authors.affiliation: GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Micheal D
authors.initials: MD
authors.lastname: Gaul
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Karen
authors.initials: K
authors.lastname: Affleck
authors.forename: G Stuart
authors.initials: GS
authors.lastname: Cockerill
authors.forename: Tona M
authors.initials: TM
authors.lastname: Gilmer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: Stephen
authors.initials: S
authors.lastname: Guntrip
authors.forename: Barry R
authors.initials: BR
authors.lastname: Keith
authors.forename: Wilson B
authors.initials: WB
authors.lastname: Knight
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mullin
authors.forename: Doris M
authors.initials: DM
authors.lastname: Murray
authors.forename: David W
authors.initials: DW
authors.lastname: Rusnak
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smith
authors.forename: Sarva
authors.initials: S
authors.lastname: Tadepalli
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Wood
authors.forename: Karen
authors.initials: K
authors.lastname: Lackey
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011799:Quinazolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases