5E2P

FACTOR XIA IN COMPLEX WITH THE INHIBITOR N-[(1S)-1-benzyl-2-[2-[5-chloro-2-(tetrazol-1-yl)phenyl]ethylamino]-2-oxo-ethyl]-4-hydroxy-2-oxo-1H-quinoline-6-carboxamide

5E2P の概要

• エントリーDOI: 10.2210/pdb5e2p/pdb
• 関連するPDBエントリー: 5E2O
• 分子名称: Coagulation factor XIa light chain, N-[(1S)-1-benzyl-2-[2-[5-chloro-2-(tetrazol-1-yl)phenyl]ethylamino]-2-oxo-ethyl]-4-hydroxy-2-oxo-1H-quinoline-6-carboxamide, 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: 28875.07

構造登録者

Wei, A. (登録日: 2015-10-01, 公開日: 2015-12-09, 最終更新日: 2024-11-06)

主引用文献

Smith, L.M.,Orwat, M.J.,Hu, Z.,Han, W.,Wang, C.,Rossi, K.A.,Gilligan, P.J.,Pabbisetty, K.B.,Osuna, H.,Corte, J.R.,Rendina, A.R.,Luettgen, J.M.,Wong, P.C.,Narayanan, R.,Harper, T.W.,Bozarth, J.M.,Crain, E.J.,Wei, A.,Ramamurthy, V.,Morin, P.E.,Xin, B.,Zheng, J.,Seiffert, D.A.,Quan, M.L.,Lam, P.Y.,Wexler, R.R.,Pinto, D.J.
Novel phenylalanine derived diamides as Factor XIa inhibitors.
Bioorg.Med.Chem.Lett., 26:472-478, 2016

PubMed Abstract: The synthesis, structural activity relationships (SAR), and selectivity profile of a potent series of phenylalanine diamide FXIa inhibitors will be discussed. Exploration of P1 prime and P2 prime groups led to the discovery of compounds with high FXIa affinity, good potency in our clotting assay (aPPT), and high selectivity against a panel of relevant serine proteases as exemplified by compound 21. Compound 21 demonstrated good in vivo efficacy (EC50=2.8μM) in the rabbit electrically induced carotid arterial thrombosis model (ECAT).

PubMed: 26704266
DOI: 10.1016/j.bmcl.2015.11.089

実験手法

X-RAY DIFFRACTION (2.11 Å)