1Y6B

Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor

1Y6B の概要

• エントリーDOI: 10.2210/pdb1y6b/pdb
• 関連するPDBエントリー: 1VR2 1Y6A
• 分子名称: Vascular endothelial growth factor receptor 2, N-(CYCLOPROPYLMETHYL)-4-(METHYLOXY)-3-({5-[3-(3-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-YL}AMINO)BENZENESULFONAMIDE (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Homo sapiens (human)
• 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: 42153.24

構造登録者

Harris, P.A.,Cheung, M.,Hunter, R.N.,Brown, M.L.,Veal, J.M.,Nolte, R.T.,Wang, L.,Liu, W.,Crosby, R.M.,Johnson, J.H.,Epperly, A.H.,Kumar, R.,Luttrell, D.K.,Stafford, J.A. (登録日: 2004-12-05, 公開日: 2005-06-07, 最終更新日: 2024-02-14)

主引用文献

Harris, P.A.,Cheung, M.,Hunter, R.N.,Brown, M.L.,Veal, J.M.,Nolte, R.T.,Wang, L.,Liu, W.,Crosby, R.M.,Johnson, J.H.,Epperly, A.H.,Kumar, R.,Luttrell, D.K.,Stafford, J.A.
Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
J.Med.Chem., 48:1610-1619, 2005

PubMed Abstract: A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.

PubMed: 15743202
DOI: 10.1021/jm049538w

実験手法

X-RAY DIFFRACTION (2.1 Å)