title: Profile and molecular modeling of 3-(indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1 H-pyrrole-2,5-dione (1) as a highly selective VEGF-R2/3 inhibitor.
abstract: We report on selectivity profiling of 1 in a panel of 20 protein kinases and molecular modeling indicating 1 to be highly active and selective for VEGF-R2/3. Sequence alignment analysis and detailed insights into the ATP binding pockets of targeted protein kinases from the panel result in a unique structural architecture of VEGF-R2 mainly caused by the hydrophobic pocket I, determining the molecular basis for activity and selectivity of 1.
authors.affiliation: Department of Pharmacy, Eberhard Karls University, Auf der Morgenstelle 8, D-72076 Tübingen, Germany. Christian.Peifer@uni-tuebingen.de
authors.forename: Christian
authors.initials: C
authors.lastname: Peifer
authors.forename: Agata
authors.initials: A
authors.lastname: Krasowski
authors.forename: Nina
authors.initials: N
authors.lastname: Hämmerle
authors.forename: Oliver
authors.initials: O
authors.lastname: Kohlbacher
authors.forename: Gerd
authors.initials: G
authors.lastname: Dannhardt
authors.forename: Frank
authors.initials: F
authors.lastname: Totzke
authors.forename: Christoph
authors.initials: C
authors.lastname: Schächtele
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000737:chemistry*
chemical_list: D007211:Indoles; D011758:Pyrroles; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3