title: Inhibition of the ras-dependent mitogenic pathway by phosphopeptide prodrugs with antiproliferative properties.
abstract: Phosphopeptide prodrugs bearing two S-acyl-2-thioethyl (SATE) biolabile phosphate protections were developed. They are capable to inhibit the Shc/Grb2 interaction and MAP kinases (ERK1 and ERK2) phosphorylation in cellular assay. The S-acetyl-2-thioethyl (MeSATE) analogue showed an IC50 of 1 microM in the inhibition of the colony formation of tumor cell line NIH3T3/HER2.
authors.affiliation: Laboratoire de Pharmacochimie Moléculaire et Structurale, U266 INSERM, UMR 8600 CNRS, Faculté de Pharmacie, Paris, France.
authors.forename: W Q
authors.initials: WQ
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Vidal
authors.forename: C
authors.initials: C
authors.lastname: Mathé
authors.forename: C
authors.initials: C
authors.lastname: Périgaud
authors.forename: C
authors.initials: C
authors.lastname: Garbay
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D051380:GRB2 Adaptor Protein; D019751:Intramolecular Transferases / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010748:Phosphopeptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D010748:Phosphopeptides; D011355:Prodrugs; D011506:Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase