title: Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors.
abstract: Various derivatives of thiazolidine-diones have been identified as tyrosine protein kinase inhibitors. The epidermal growth factor (EGF) receptor kinase and c-src kinase were inhibited in vitro with IC50 values in the range of 1-7 microM. The v-abl tyrosine protein kinase was not inhibited by thiazolidine-diones. Inhibition was found to be specific for tyrosine protein kinases. Inhibition of serine/threonine protein kinases was not observed. The active derivatives were shown to inhibit EGF-induced receptor autophosphorylation, either in vitro or in intact cells, and were also found to inhibit growth of the EGF-dependent BALB/MK and A431 cell lines (IC50 1-3 microM). Growth of the interleukin-3-dependent myeloid cell line FDC-P1 was inhibited with equal efficiency. Thus, in these cell lines, members of the c-src kinase family are also potential targets for inhibition by the compounds.
authors.affiliation: Oncology and Virology Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
authors.forename: J F
authors.initials: JF
authors.lastname: Geissler
authors.forename: P
authors.initials: P
authors.lastname: Traxler
authors.forename: U
authors.initials: U
authors.lastname: Regenass
authors.forename: B J
authors.initials: BJ
authors.lastname: Murray
authors.forename: J L
authors.initials: JL
authors.lastname: Roesel
authors.forename: T
authors.initials: T
authors.lastname: Meyer
authors.forename: E
authors.initials: E
authors.lastname: McGlynn
authors.forename: A
authors.initials: A
authors.lastname: Storni
authors.forename: N B
authors.initials: NB
authors.lastname: Lydon
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D007202:Indicators and Reagents; D047428:Protein Kinase Inhibitors; D013844:Thiazoles; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases