The natural bioactive compound damnacanthal inhibits several tyrosine kinases. Herein, we
show that -in fact- damancanthal is a multi kinase inhibitor. A docking and molecular dynamics
simulation approach allows getting further insight on the inhibitory effect of damnacanthal on
three different kinases: vascular endothelial growth factor receptor-2, c-Met and focal adhesion
kinase. Several of the kinases targeted and inhibited by damnacanthal are involved in
angiogenesis. Ex vivo and in vivo experiments clearly demonstrate that, indeed, damnacanthal
is a very potent inhibitor of angiogenesis. A number of in vitro assays contribute to determine
the specific effects of damnacanthal on each of the steps of the angiogenic process, including
inhibition of tubulogenesis, endothelial cell proliferation, survival, migration and production of
extracellular matrix remodeling enzyme. Taken altogether, these results suggest that
damancanthal could have potential interest for the treatment of cancer and other angiogenesisdependent
diseases.
