title: Dual IGF-1R/SRC inhibitors based on a N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide structure.
abstract: The N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide motif was identified as a novel scaffold for the development of kinase inhibitors. Derivatives with a biphenyl element attached to the hydrazide structure proved to be submicromolar dual inhibitors of the cancer-related kinases IGF-1R and SRC. One of the most potent kinase inhibitors of the series produced a selective growth inhibition in a panel of cultivated cancer cell lines.
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schmidt
authors.forename: Lutz
authors.initials: L
authors.lastname: Preu
authors.forename: Thomas
authors.initials: T
authors.lastname: Lemcke
authors.forename: Frank
authors.initials: F
authors.lastname: Totzke
authors.forename: Christoph
authors.initials: C
authors.lastname: Schächtele
authors.forename: Michael H G
authors.initials: MH
authors.lastname: Kubbutat
authors.forename: Conrad
authors.initials: C
authors.lastname: Kunick
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D006834:Hydrazines; D007211:Indoles; D047428:Protein Kinase Inhibitors; D017526:Receptor, IGF Type 1; D019061:src-Family Kinases