4YT6

Factor VIIa in complex with the inhibitor 4-{[(R)-[5-ethoxy-2-fluoro-3-(propan-2-yloxy)phenyl](4-phenyl-1H-imidazol-2-yl)methyl]amino}benzenecarboximidamide

4YT6 の概要

• エントリーDOI: 10.2210/pdb4yt6/pdb
• 関連するPDBエントリー: 4YT7
• 分子名称: Coagulation factor VII (heavy chain), Coagulation factor VII (light chain), 4-[[(R)-(5-ethoxy-2-fluoranyl-3-propan-2-yloxy-phenyl)-(4-phenyl-1H-imidazol-2-yl)methyl]amino]benzenecarboximidamide, ... (7 entities in total)
• 機能のキーワード: glycoprotein, hydrolase, serine protease, plasma, blood coagulation factor, protein inhibitor complex, calcium-binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P08709 P08709
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35563.55

構造登録者

Wei, A. (登録日: 2015-03-17, 公開日: 2015-04-29, 最終更新日: 2024-10-09)

主引用文献

Glunz, P.W.,Cheng, X.,Cheney, D.L.,Weigelt, C.A.,Wei, A.,Luettgen, J.M.,Wong, P.C.,Wexler, R.R.,Priestley, E.S.
Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.
Bioorg.Med.Chem.Lett., 25:2169-2173, 2015

PubMed Abstract: Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring forms key hydrophobic interactions with the S1' pocket. Exploration of phenylimidazole substitution led to the discovery of potent, selective and efficacious inhibitors of TF-FVIIa.

PubMed: 25881820
DOI: 10.1016/j.bmcl.2015.03.062

実験手法

X-RAY DIFFRACTION (2.07 Å)