4NA9

Factor VIIa in complex with the inhibitor 3'-amino-5'-[(2s,4r)-6-carbamimidoyl-4-phenyl-1,2,3,4-tetrahydroquinolin-2-yl]biphenyl-2-carboxylic acid

Summary for 4NA9

• Entry DOI: 10.2210/pdb4na9/pdb
• Descriptor: Coagulation factor VII heavy chain, Coagulation factor VII light chain, 3'-amino-5'-[(2S,4R)-6-carbamimidoyl-4-phenyl-1,2,3,4-tetrahydroquinolin-2-yl]biphenyl-2-carboxylic acid, ... (5 entities in total)
• Functional Keywords: serine protease, hydrolase, plasma, blood coagulation factor, protein inhibitor complex, calcium-binding, glycoprotein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P08709 P08709
• Total number of polymer chains: 2
• Total formula weight: 34636.70

Authors

Wei, A. (deposition date: 2013-10-21, release date: 2014-02-12, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.24 Å)