4JYU

Structure of factor VIIA in complex with the inhibitor (2R)-2-[(1-AMINOISOQUINOLIN-6-YL)AMINO]-2-[3-ETHOXY-4-(PROPAN-2-YLOXY)PHENYL]-N-(PHENYLSULFONYL)ETHANAMIDE

4JYU の概要

• エントリーDOI: 10.2210/pdb4jyu/pdb
• 関連するPDBエントリー: 4JYV
• 分子名称: Factor VII light chain, Factor VII heavy chain, (2R)-2-[(1-aminoisoquinolin-6-yl)amino]-2-[3-ethoxy-4-(propan-2-yloxy)phenyl]-N-(phenylsulfonyl)ethanamide, ... (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: 35461.42

構造登録者

Wei, A.,Anumula, R. (登録日: 2013-04-01, 公開日: 2013-07-24, 最終更新日: 2024-11-06)

主引用文献

Glunz, P.W.,Zhang, X.,Zou, Y.,Delucca, I.,Nirschl, A.H.,Cheng, X.,Weigelt, C.A.,Cheney, D.L.,Wei, A.,Anumula, R.,Luettgen, J.M.,Rendina, A.R.,Harpel, M.,Luo, G.,Knabb, R.,Wong, P.C.,Wexler, R.R.,Priestley, E.S.
Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.
Bioorg.Med.Chem.Lett., 23:5244-5248, 2013

PubMed Abstract: Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.

PubMed: 23845220
DOI: 10.1016/j.bmcl.2013.06.027

実験手法

X-RAY DIFFRACTION (1.8 Å)