Ulrike Schmidt (firstname.lastname@example.org)
Jessica Ahmed (email@example.com)
Elke Michalsky (firstname.lastname@example.org)
Michael Hoepfner (email@example.com)
Robert Preissner (firstname.lastname@example.org)
 Structural Bioinformatics Group, Institute for Molecular Biology and Bioinformatics, Charite (CBF), Arnimallee 22, 14195 Berlin, Germany
 Molecular Tumor Therapy and Tumor Angiogenesis Group, Institute of Physiology, Charite (CBF), Arnimallee 22, 14195 Berlin, Germany
The Vascular Endothelial Growth Factor receptors (VEGF-Rs) play a significant role in tumor development and tumor angiogenesis and are therefore interesting targets in cancer therapy. Targeting the VEGF-R is of special importance as the feed of the tumor has to be reduced. In general, this can be carried out by inhibiting the tyrosine kinase function of the VEGF-R. Nevertheless, there arise some problems with the specificity of known kinase inhibitors: they bind to the ATP-binding site and inhibit a number of kinases, moreover the so far most specific inhibitors act at least on these three major types of VEGF-Rs: Flt-1, Flk-1/KDR, Flt-4. The goal is a selective VEGF-R-2 (Flk-1/KDR) inhibitor, because this receptor triggers rather unspecific signals from VEGF-A, -C, -D and -E. Here, we describe a protocol starting from an established inhibitor (Vatalanib) with 2D-/3Dsearching and property filtering of the in silico screening hits and the “negative docking approach”. With this approach we were able to identify a compound, which shows a fourfold higher reduction of the proliferation rate of endothelial cells compared to the reduction effect of the lead structure.