5EGM

Development of a novel tricyclic class of potent and selective FIXa inhibitors

5EGM の概要

• エントリーDOI: 10.2210/pdb5egm/pdb
• 分子名称: Coagulation factor IX, SODIUM ION, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (6 entities in total)
• 機能のキーワード: serine proteinase, blood coagulation, coagulation factor, hydrolase-2 hydrolase inhibitor complex, 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 : P00740 P00740
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33726.81

構造登録者

Meng, D.,Andre, P.,Bateman, T.J.,Berger, R.,Chen, Y.,Desai, K.,Dewnani, S.,Ellsworth, K.,Feng, D.,Geissler, W.M.,Guo, L.,Hruza, A.,Jian, T.,Li, H.,Parker, D.L.,Reichert, P.,Sherer, E.C.,Smith, C.J.,Sonatore, L.M.,Tschirret-Guth, R.,Wu, J.,Xu, J.,Zhang, T.,Campeau, L.,Orr, R.,Poirier, M.,McCabe-Dunn, j.,Araki, K.,Nishimura, T.,Sakurada, I.,Hirabayashi, T.,Wood, H.B. (登録日: 2015-10-27, 公開日: 2015-11-18, 最終更新日: 2024-11-20)

主引用文献

Meng, D.,Andre, P.,Bateman, T.J.,Berger, R.,Chen, Y.H.,Desai, K.,Dewnani, S.,Ellsworth, K.,Feng, D.,Geissler, W.M.,Guo, L.,Hruza, A.,Jian, T.,Li, H.,Metzger, J.,Parker, D.L.,Reichert, P.,Sherer, E.C.,Smith, C.J.,Sonatore, L.M.,Tschirret-Guth, R.,Wu, J.,Xu, J.,Zhang, T.,Campeau, L.C.,Orr, R.,Poirier, M.,McCabe-Dunn, J.,Araki, K.,Nishimura, T.,Sakurada, I.,Hirabayashi, T.,Wood, H.B.
Development of a novel tricyclic class of potent and selective FIXa inhibitors.
Bioorg.Med.Chem.Lett., 25:5437-5443, 2015

PubMed Abstract: Using structure based drug design, a novel class of potent coagulation factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds were evaluated in rat IV/PO pharmacokinetic (PK) studies and demonstrated desirable oral PK profiles. Finally, the pharmacodynamics (PD) of this class of molecules were evaluated in thrombin generation assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor.

PubMed: 26318999
DOI: 10.1016/j.bmcl.2015.07.078

実験手法

X-RAY DIFFRACTION (1.841 Å)