4ISI

Structure of FACTOR VIIA in complex with the inhibitor (6S)-N-(4-CARBAMIMIDOYLBENZYL)-1-CHLORO-3-(CYCLOBUTYLAMINO)-8,8-DIETHYL-4-OXO-4,6,7,8-TETRAHYDROPYRROLO[1,2-A]PYRAZINE-6-CARBOXAMIDE

4ISI の概要

• エントリーDOI: 10.2210/pdb4isi/pdb
• 関連するPDBエントリー: 4ISH
• 分子名称: Factor VII heavy chain, Factor VII light chain, (6S)-N-(4-carbamimidoylbenzyl)-1-chloro-3-(cyclobutylamino)-8,8-diethyl-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrazine-6-carboxamide, ... (5 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: 34645.16

構造登録者

Wei, A. (登録日: 2013-01-16, 公開日: 2013-02-27, 最終更新日: 2024-11-06)

主引用文献

Zhang, X.,Glunz, P.W.,Jiang, W.,Schmitt, A.,Newman, M.,Barbera, F.A.,Bozarth, J.M.,Rendina, A.R.,Wei, A.,Wen, X.,Rossi, K.A.,Luettgen, J.M.,Wong, P.C.,Knabb, R.M.,Wexler, R.R.,Scott Priestley, E.
Design and synthesis of bicyclic pyrazinone and pyrimidinone amides as potent TF-FVIIa inhibitors.
Bioorg.Med.Chem.Lett., 23:1604-1607, 2013

PubMed Abstract: Bicyclic pyrazinone and pyrimidinone amides were designed and synthesized as potent TF-FVIIa inhibitors. SAR demonstrated that the S2 and S3 pockets of FVIIa prefer to bind small, lipophilic groups. An X-ray crystal structure of optimized compound 9b bound in the active site of FVIIa showed that the bicyclic scaffold provides 5 hydrogen bonding interactions in addition to projecting groups for interactions within the S1, S2 and S3 pockets. Compound 9b showed excellent FVIIa potency, good selectivity against FIXa, Xa, XIa and chymotrypsin, and good clotting activity.

PubMed: 23416003
DOI: 10.1016/j.bmcl.2013.01.094

実験手法

X-RAY DIFFRACTION (1.94 Å)