3B8Q

Crystal structure of the VEGFR2 kinase domain in complex with a naphthamide inhibitor

3B8Q の概要

• エントリーDOI: 10.2210/pdb3b8q/pdb
• 関連するPDBエントリー: 3B8R
• 分子名称: Vascular endothelial growth factor receptor 2, N-(4-chlorophenyl)-6-[(6,7-dimethoxyquinolin-4-yl)oxy]naphthalene-1-carboxamide (3 entities in total)
• 機能のキーワード: receptor tyrosine kinase, angiogenesis, atp-binding, developmental protein, differentiation, glycoprotein, host-virus interaction, immunoglobulin domain, membrane, nucleotide-binding, phosphorylation, polymorphism, transferase, transmembrane, tyrosine-protein kinase
• 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: 2
• 化学式量合計: 73539.03

構造登録者

Whittington, D.A.,Long, A.M.,Gu, Y.,Zhao, H. (登録日: 2007-11-01, 公開日: 2008-04-01, 最終更新日: 2024-10-30)

主引用文献

Harmange, J.C.,Weiss, M.M.,Germain, J.,Polverino, A.J.,Borg, G.,Bready, J.,Chen, D.,Choquette, D.,Coxon, A.,DeMelfi, T.,DiPietro, L.,Doerr, N.,Estrada, J.,Flynn, J.,Graceffa, R.F.,Harriman, S.P.,Kaufman, S.,La, D.S.,Long, A.,Martin, M.W.,Neervannan, S.,Patel, V.F.,Potashman, M.,Regal, K.,Roveto, P.M.,Schrag, M.L.,Starnes, C.,Tasker, A.,Teffera, Y.,Wang, L.,White, R.D.,Whittington, D.A.,Zanon, R.
Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis and Evaluation
J.Med.Chem., 51:1649-1667, 2008

PubMed Abstract: A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.

PubMed: 18324761
DOI: 10.1021/jm701097z

実験手法

X-RAY DIFFRACTION (2.75 Å)