2OH4

Crystal structure of Vegfr2 with a benzimidazole-urea inhibitor

2OH4 の概要

• エントリーDOI: 10.2210/pdb2oh4/pdb
• 関連するPDBエントリー: 1vr2 1y6a 1y6b 1ywm
• 分子名称: Vascular endothelial growth factor receptor 2, SULFATE ION, METHYL (5-{4-[({[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-1H-BENZIMIDAZOL-2-YL)CARBAMATE, ... (4 entities in total)
• 機能のキーワード: vascular endothelial growth factor receptor 2, tyrosine-protein kinase, angiogenesis, atp-binding, phosphorylation, kinase insert domain receptor, protein-tyrosine kinase receptor flk-1, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell junction . Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted . Isoform 3: Secreted: P35968
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37104.21

構造登録者

Nolte, R.T.,Wang, L. (登録日: 2007-01-09, 公開日: 2007-09-18, 最終更新日: 2024-10-16)

主引用文献

Hasegawa, M.,Nishigaki, N.,Washio, Y.,Kano, K.,Harris, P.A.,Sato, H.,Mori, I.,West, R.I.,Shibahara, M.,Toyoda, H.,Wang, L.,Nolte, R.T.,Veal, J.M.,Cheung, M.
Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors.
J.Med.Chem., 50:4453-4470, 2007

PubMed Abstract: We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.

PubMed: 17676829
DOI: 10.1021/jm0611051

実験手法

X-RAY DIFFRACTION (2.05 Å)