4ZAE

Development of a novel class of potent and selective FIXa inhibitors

Summary for 4ZAE

• Entry DOI: 10.2210/pdb4zae/pdb
• Descriptor: Coagulation factor IX, 2,6-dichloro-N-[(2R)-2-(5,6-dimethyl-1H-benzimidazol-2-yl)-2-phenylethyl]-4-(4H-1,2,4-triazol-4-yl)benzamide, SODIUM ION, ... (6 entities in total)
• Functional Keywords: serine proteinase, blood coagulation, coagulation factor, 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: 33682.19

Authors

Hruza, A.,Reichert, P. (deposition date: 2015-04-13, release date: 2015-06-03, Last modification date: 2024-10-16)

Primary citation

Zhang, T.,Andre, P.,Bateman, T.J.,Chen, Y.H.,Desai, K.,Ellsworth, K.,Geissler, W.M.,Guo, L.,Hruza, A.,Jian, T.,Meng, D.,Parker, D.L.,Qian, X.,Reichert, P.,Sherer, E.C.,Shu, M.,Smith, C.J.,Sonatore, L.M.,Tschirret-Guth, R.,Nolting, A.F.,Orr, R.,Campeau, L.C.,Araki, K.,Nishimura, T.,Sakurada, I.,Wood, H.B.
Development of a novel class of potent and selective FIXa inhibitors.
Bioorg.Med.Chem.Lett., 25:4945-4949, 2015

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

PubMed: 25978966
DOI: 10.1016/j.bmcl.2015.04.057

Experimental method

X-RAY DIFFRACTION (1.86 Å)