Inhibition of the ras-dependent mitogenic pathway by phosphopeptide prodrugs with antiproliferative properties.
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.
Liu
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WQ
Laboratoire de Pharmacochimie Moléculaire et Structurale, U266 INSERM, UMR 8600 CNRS, Faculté de Pharmacie, Paris, France.
Vidal
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Mathé
C
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Périgaud
C
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Garbay
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C
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
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