title: Three stories on Eph kinase inhibitors: From in silico discovery to in vivo validation.
abstract: Several selective and potent EphB4 inhibitors have been discovered, optimized and biophysically characterized by our groups over the past years. On the outset of these discoveries high throughput docking techniques were applied. Herein, we review the optimization campaigns started from three of these hits (Xan-A1, Pyr-A1 and Qui-A1) with emphasis on their in depth in vitro and in vivo characterization, together with previously unpublished angiogenesis and fluorescence based assays.
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Unzue
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Karine
authors.initials: K
authors.lastname: Lafleur
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Kolb
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Ludwig Maximilians University Münich, Butenandtstrasse 5-13, 81377 Münich, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Liebl
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Ludwig Maximilians University Münich, Butenandtstrasse 5-13, 81377 Münich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahler
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Electronic address: caflisch@bioc.uzh.ch.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Electronic address: cristina.nevado@chem.uzh.ch.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nevado
mesh_terms: D000818:Animals; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology; D036183:Receptor, EphB2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D019820:Xanthine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; C000608165:pyrrolo(2,3-b)quinoxaline; D019820:Xanthine; D036183:Receptor, EphB2
keywords: Drug discovery; EphB4; In silico; Kinase; Potency; Selectivity