4Y79

Factor Xa complex with GTC000406

Summary for 4Y79

• Entry DOI: 10.2210/pdb4y79/pdb
• Descriptor: Coagulation factor X, CALCIUM ION, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: hydrolase, inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 44267.70

Authors

Convery, M.A.,Young, R.J.,Senger, S.,Hamblin, J.N.,Chan, C.,Toomey, J.R.,Watson, N.S. (deposition date: 2015-02-13, release date: 2015-09-30, Last modification date: 2024-11-06)

Primary citation

Chan, C.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Campbell, M.,Chaudry, L.,Chung, C.W.,Convery, M.A.,Hamblin, J.N.,Johnstone, L.,Kelly, H.A.,Kleanthous, S.,Patikis, A.,Patel, C.,Pateman, A.J.,Senger, S.,Shah, G.P.,Toomey, J.R.,Watson, N.S.,Weston, H.E.,Whitworth, C.,Young, R.J.,Zhou, P.
Factor Xa inhibitors: S1 binding interactions of a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides.
J. Med. Chem., 50:1546-1557, 2007

PubMed Abstract: Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.

PubMed: 17338508
DOI: 10.1021/jm060870c

Experimental method

X-RAY DIFFRACTION (2.1 Å)