Inhibition of the ras-dependent mitogenic pathway by phosphopeptide prodrugs with antiproliferative properties

Bioorg Med Chem Lett. 2000 Apr 3;10(7):669-72. doi: 10.1016/s0960-894x(00)00077-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • GRB2 Adaptor Protein
  • Intramolecular Transferases / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphopeptides / chemistry
  • Phosphopeptides / pharmacology*
  • Phosphorylation / drug effects
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Proteins / metabolism
  • Stem Cells / drug effects
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / pharmacology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Phosphopeptides
  • Prodrugs
  • Proteins
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • ras Proteins
  • Intramolecular Transferases
  • squalene-hopene cyclase