Phytochemistry Reviews

, Volume 13, Issue 1, pp 191–206 | Cite as

Plant-derived vascular disrupting agents: compounds, actions, and clinical trials

  • Verena K. Kretzschmann
  • Robert Fürst


The tumor vasculature of solid tumors offers unique characteristics compared to the normal vasculature and, therefore, represents an attractive target in anti-cancer therapy. Besides the classic anti-angiogenic agents, which inhibit tumor neovascularization, a novel promising class of anti-tumor drugs has emerged in the last years, the vascular-disrupting agents (VDAs). In contrast to angiogenesis inhibitors, VDAs act on already established tumor blood vessels of large solid tumors and induce a vascular shutdown by targeting tumor endothelial cells. This results in extensive necrotic tumor cell death. The sources of VDAs are quite divers, however, the plant-derived compounds represent the largest and most prominent class. Plant-derived VDAs have undergone extensive preclinical investigations and are now tested in several advanced clinical trials. In this review we summarize preclinical data, including drug-target relationships as well as functional in vitro and in vivo assays, discuss their molecular way of action, and update the clinical status of the most prominent plant-derived VDAs: FAA/DMXAA, CA-4-P, OXi4503, AVE8062, and ZD6126. All these data emphasize the value of secondary plant metabolites and their (semi-)synthetic derivatives for current drug discovery.


Anti-vascular therapy Cancer Combretastatin DMXAA Tubulin-binding drugs 



Angiogenesis inhibitor


Anaplastic thyroid cancer


Combretastatin A-4


Combretastatin A-4 3-O-phosphate


Dynamic contrast-enhanced magnetic resonance imaging


Dose-limiting toxicity


5, 6-Dimethylxanthenone-4-acetic acid


Flavone acetic acid


Guanine nucleotide exchange factor


Human lung microvascular endothelial cells


Highest non-lethal dose


Human umbilical vein endothelial cells


IκB kinase


Inhibitor of NFκB


Myosin light chain


Maximum tolerated dose




Nuclear factor κB


Non-small cell lung cancer




Positron emission tomography




Recommended dose


Rho kinase


Tumor necrosis factor


Vascular-disrupting agent



We are thankful to Dr. Ilse Zündorf (Goethe-University Frankfurt/Main, Germany) for her help with preparing the figures.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Pharmacy, Center for Drug Research, Pharmaceutical BiologyUniversity of MunichMunichGermany
  2. 2.Institute of Pharmaceutical Biology, BiocenterGoethe-University Franfurt/MainFrankfurt/MainGermany

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