4NA7

Factor XIA in complex with the inhibitor 3'-[(2S,4R)-6-carbamimidoyl-4-methyl-4-phenyl-1,2,3,4-tetrahydroquinolin-2-yl]-4-carbamoyl-5'-[(3-methylbutanoyl)amino]biphenyl-2-carboxylic acid

Summary for 4NA7

• Entry DOI: 10.2210/pdb4na7/pdb
• Related: 4NA8 4NA9
• Descriptor: Coagulation factor XI, 3'-[(2S,4R)-6-carbamimidoyl-4-methyl-4-phenyl-1,2,3,4-tetrahydroquinolin-2-yl]-4-carbamoyl-5'-[(3-methylbutanoyl)amino]biphenyl-2-carboxylic acid, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase, serine protease, blood coagulation factor, protein inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P03951
• Total number of polymer chains: 1
• Total formula weight: 28593.34

Authors

Wei, A. (deposition date: 2013-10-21, release date: 2014-02-12, Last modification date: 2024-11-20)

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 (2.8 Å)