Selective anti-endothelial effects of protracted low-dose BAL-9504, a novel geranylgeranyl-transferase inhibitor

Eur J Pharmacol. 2003 Sep 5;477(1):17-21. doi: 10.1016/j.ejphar.2003.08.001.


Because the anti-endothelial effects of agents such as interferon alpha, endostatin, and various chemotherapeutic drugs appear to be optimal after protracted, frequent dosing, both in vitro and in vivo, using low concentrations/doses of drugs, we tested the geranylgeranyl transferase inhibitor BAL-9504 ((E,E,E) [2-oxo-2-[[(3,7,11,15-tetramethyl-2,6,10,14 hexadecatetraenyl)-oxy]amino]ethyl] phosphonic acid) in this manner on different human cell types, including endothelial, breast cancer cells and fibroblasts. We found that human endothelial cells were preferentially affected with respect to inhibition of proliferation, induction of apoptosis, suppression of adhesion to fibronectin, and blockade of cell migration, by daily exposure to low concentrations of BAL-9504 for 6 days. These results may have implications in terms of both increasing anti-tumor efficacy, mediated by antiangiogenic mechanisms, and reducing toxic side effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Apoptosis / drug effects
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Fibronectins / chemistry
  • Humans
  • Organophosphonates / administration & dosage
  • Organophosphonates / pharmacology*
  • Umbilical Cord / cytology


  • Angiogenesis Inhibitors
  • BAL 9504
  • Fibronectins
  • Organophosphonates
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I