4NA8

Factor XIa in complex with the inhibitor 5-aminocarbonyl-2-[3-[(2s,4r)-6-carbamimidoyl-4-methyl-4-phenyl-2,3-dihydro-1h-quinolin-2-yl]phenyl]benzoic acid

4NA8 の概要

• エントリーDOI: 10.2210/pdb4na8/pdb
• 分子名称: Coagulation factor XI, 5-aminocarbonyl-2-[3-[(2S,4R)-6-carbamimidoyl-4-methyl-4-phenyl-2,3-dihydro-1H-quinolin-2-yl]phenyl]benzoic acid, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, serine protease, blood coagulation factor, protein inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P03951
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28426.22

構造登録者

Wei, A. (登録日: 2013-10-21, 公開日: 2014-02-12, 最終更新日: 2024-10-30)

主引用文献

Quan, M.L.,Wong, P.C.,Wang, C.,Woerner, F.,Smallheer, J.M.,Barbera, F.A.,Bozarth, J.M.,Brown, R.L.,Harpel, M.R.,Luettgen, J.M.,Morin, P.E.,Peterson, T.,Ramamurthy, V.,Rendina, A.R.,Rossi, K.A.,Watson, C.A.,Wei, A.,Zhang, G.,Seiffert, D.,Wexler, R.R.
Tetrahydroquinoline Derivatives as Potent and Selective Factor XIa Inhibitors.
J.Med.Chem., 57:955-969, 2014

PubMed Abstract: Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a potent and selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models and did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor.

PubMed: 24405333
DOI: 10.1021/jm401670x

実験手法

X-RAY DIFFRACTION (2.3 Å)