Este es el manuscrito que fue aceptado y que finalmente se publicó en Cancer Letters con el DOI: 10.1016/j.canlet.2016.10.037The 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.Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507
(Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian
Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII
(Spain). JAGV had the financial support of Vicerrectorado de Investigación y
Transferencia (University of Málaga, Spain). The funders had no role in the study
design, data collection and analysis, decision to publish or preparation of the
manuscript
