title: Limited selectivity of a synthetic erbstatin derivative for tyrosine kinase and cell growth inhibition.
abstract: The natural tyrosine kinase inhibitor erbstatin and a synthetic analog (1302) were co0pared for their inhibitory activity on EGF receptor kinase, PDGF receptor kinase and a src-type kinase from bovine brain. Erbstatin inhibited both growth factor receptor kinases equally well and had little effect on the src kinase. The analog exhibited similar potency for inhibition of purified EGF receptor tyrosine kinase as erbstatin, however, was clearly less effective for inhibition of purified PDGF receptor kinase as well as the src-type kinase. The selectivity was, however, not seen when the derivative was assayed with respect to inhibition of autophosphorylation of both growth factor receptors in Swiss 3T3 cell membranes. The latter finding might explain a lack of selectivity of the compound for inhibition of DNA synthesis in 3T3 cells when the cells were stimulated comparatively with EGF, insulin, EGF plus insulin or PDGF. The results suggest that the environment of growth factor receptors in the cell membrane can remarkably modify their susceptibility to tyrosine kinase inhibitors.
authors.affiliation: Department of Cellular Biochemistry, Central Institute of Molecular Biology, BerlinBuch, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Treuner
authors.forename: F D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: W
authors.initials: W
authors.lastname: Schulze
authors.forename: S P
authors.initials: SP
authors.lastname: Petuchov
authors.forename: R
authors.initials: R
authors.lastname: Grosse
mesh_terms: D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D066246:ErbB Receptors / Q000378:metabolism; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor
chemical_list: D006873:Hydroquinones; D047428:Protein Kinase Inhibitors; D011956:Receptors, Cell Surface; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; C048212:erbstatin