Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4

Bioorg Med Chem Lett. 2003 May 5;13(9):1505-8. doi: 10.1016/s0960-894x(03)00206-3.


Combretastatin A-4 disodiumphosphate (CA4P), a prodrug formulation of the natural product combretastatin A-4 (CA4), is currently in clinical investigation for the treatment of cancer. In vivo, CA4P is rapidly enzymatically converted to CA4, a potent inhibitor of tubulin polymerization (IC(50)=1-2 microM), and rapidly causes bloodflow shutdown in tumor tissues. A variety of alkyl and aryl di- and triesters of CA4P have been synthesized and evaluated as potential CA4 prodrugs and/or stable CA4P analogues.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Organophosphates / chemical synthesis*
  • Organophosphates / pharmacology
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology
  • Stilbenes / chemistry*
  • Stilbenes / metabolism


  • Angiogenesis Inhibitors
  • Organophosphates
  • Prodrugs
  • Stilbenes
  • fosbretabulin