title: Steering target selectivity and potency by fragment-based de novo drug design.
abstract: Kinase inhibitors: Ligand-based de novo design is validated as a viable technology for rapidly generating innovative compounds possessing the desired biochemical profile. The study discloses the discovery of the most selective vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor (right in scheme) known to date as prime lead for antiangiogenic drug development.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, Wolfgang-Pauli-Str. 10, 8093 Zürich (Switzerland).
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kudoh
authors.forename: Filip
authors.initials: F
authors.lastname: Roudnicky
authors.forename: Yi Fan
authors.initials: YF
authors.lastname: Lim
authors.forename: Yen-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Christian P
authors.initials: CP
authors.lastname: Koch
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: VEGFR; drug design; drug discovery; fragment-based design; kinase inhibitors