bioRxiv preprint doi: https://doi.org/10.1101/678896; this version posted September 9, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Structure-based drug repositioning explains ibrutinib as VEGFR2 inhibitor Melissa F. Adasme1,Y, Daniele Parisi2,Y, Kristien Van Belle3, Sebastian Salentin1, V. Joachim Haupt1,7, Gary S. Jennings1, J¨org-ChristianHeinrich1, Jean Herman3,4,5, Ben Sprangers3,4,6, Thierry Louat3, Yves Moreau2, Michael Schroeder1,* 1 Biotechnology Center (BIOTEC), Technische Universit¨atDresden, 01307 Dresden, Germany 2 ESAT-STADIUS, KU Leuven, B-3001 Heverlee, Belgium 3 Interface Valorisation Platform (IVAP), KU Leuven, 3000 Leuven, Belgium 4 Laboratory of Molecular Immunology (Rega institute), KU Leuven, Belgium 5 Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, 3000 Leuven, Belgium 6 Department of Nephrology, University Hospitals Leuven, 3000 Leuven, Belgium 7 PharmAI GmbH, 01307 Dresden, Germany YThese authors contributed equally to this work. *
[email protected] Abstract Many drugs are promiscuous and bind to multiple targets. On the one hand, these targets may be linked to unwanted side effects, but on the other, they may achieve a combined desired effect (polypharmacology) or represent multiple diseases (drug repositioning). With the growth of 3D structures of drug-target complexes, it is today possible to study drug promiscuity at the structural level and to screen vast amounts of drug-target interactions to predict side effects, polypharmacological potential, and repositioning opportunities.