2EA4

h-MetAP2 complexed with A797859

2EA4 の概要

• エントリーDOI: 10.2210/pdb2ea4/pdb
• 関連するPDBエントリー: 1YW7 1YW8 1YW9 2EA2 2GA2
• 分子名称: Methionine aminopeptidase 2, MANGANESE (II) ION, 2-(2-AMINOETHOXY)-3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}BENZOIC ACID, ... (4 entities in total)
• 機能のキーワード: protein-ligand complex, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41862.29

構造登録者

Park, C.H. (登録日: 2007-01-30, 公開日: 2008-02-05, 最終更新日: 2024-11-06)

主引用文献

Wang, G.T.,Mantei, R.A.,Kawai, M.,Tedrow, J.S.,Barnes, D.M.,Wang, J.,Zhang, Q.,Lou, P.,Garcia, L.A.,Bouska, J.,Yates, M.,Park, C.,Judge, R.A.,Lesniewski, R.,Sheppard, G.S.,Bell, R.L.
Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids
Bioorg.Med.Chem.Lett., 17:2817-2822, 2007

PubMed Abstract: A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH(3), CH(3), and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn(2+) but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl phenyl ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.

PubMed: 17350258
DOI: 10.1016/j.bmcl.2007.02.062

実験手法

X-RAY DIFFRACTION (2.35 Å)