5E2P

FACTOR XIA IN COMPLEX WITH THE INHIBITOR N-[(1S)-1-benzyl-2-[2-[5-chloro-2-(tetrazol-1-yl)phenyl]ethylamino]-2-oxo-ethyl]-4-hydroxy-2-oxo-1H-quinoline-6-carboxamide

Summary for 5E2P

• Entry DOI: 10.2210/pdb5e2p/pdb
• Related: 5E2O
• Descriptor: Coagulation factor XIa light chain, N-[(1S)-1-benzyl-2-[2-[5-chloro-2-(tetrazol-1-yl)phenyl]ethylamino]-2-oxo-ethyl]-4-hydroxy-2-oxo-1H-quinoline-6-carboxamide, SULFATE ION, ... (5 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: 28875.07

Authors

Wei, A. (deposition date: 2015-10-01, release date: 2015-12-09, Last modification date: 2016-01-20)

Primary citation

Smith, L.M.,Orwat, M.J.,Hu, Z.,Han, W.,Wang, C.,Rossi, K.A.,Gilligan, P.J.,Pabbisetty, K.B.,Osuna, H.,Corte, J.R.,Rendina, A.R.,Luettgen, J.M.,Wong, P.C.,Narayanan, R.,Harper, T.W.,Bozarth, J.M.,Crain, E.J.,Wei, A.,Ramamurthy, V.,Morin, P.E.,Xin, B.,Zheng, J.,Seiffert, D.A.,Quan, M.L.,Lam, P.Y.,Wexler, R.R.,Pinto, D.J.
Novel phenylalanine derived diamides as Factor XIa inhibitors.
Bioorg.Med.Chem.Lett., 26:472-478, 2016

PubMed Abstract: The synthesis, structural activity relationships (SAR), and selectivity profile of a potent series of phenylalanine diamide FXIa inhibitors will be discussed. Exploration of P1 prime and P2 prime groups led to the discovery of compounds with high FXIa affinity, good potency in our clotting assay (aPPT), and high selectivity against a panel of relevant serine proteases as exemplified by compound 21. Compound 21 demonstrated good in vivo efficacy (EC50=2.8μM) in the rabbit electrically induced carotid arterial thrombosis model (ECAT).

PubMed: 26704266
DOI: 10.1016/j.bmcl.2015.11.089

Experimental method

X-RAY DIFFRACTION (2.11 Å)