5EGM

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

Summary for 5EGM

• Entry DOI: 10.2210/pdb5egm/pdb
• Descriptor: Coagulation factor IX, SODIUM ION, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (6 entities in total)
• Functional Keywords: serine proteinase, blood coagulation, coagulation factor, hydrolase-2 hydrolase inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted : P00740 P00740
• Total number of polymer chains: 2
• Total formula weight: 33726.81

Authors

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. (deposition date: 2015-10-27, release date: 2015-11-18, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.841 Å)