2W26

Factor Xa in complex with BAY59-7939

Summary for 2W26

• Entry DOI: 10.2210/pdb2w26/pdb
• Related: 1C5M 1EZQ 1F0R 1F0S 1FAX 1FJS 1G2L 1G2M 1HCG 1IOE 1IQE 1IQF 1IQG 1IQH 1IQI 1IQJ 1IQK 1IQL 1IQM 1IQN 1KSN 1KYE 1LPG 1LPK 1LPZ 1LQD 1MQ5 1MQ6 1MSX 1NFU 1NFW 1NFX 1NFY 1NL8 1P0S 1V3X 1WU1 1XKA 1XKB 1Z6E 2BMG 2BOH 2BOK 2BQ6 2BQ7 2BQW 2CJI 2FZZ 2G00 2GD4 2J2U 2J34 2J38 2J4I 2J94 2J95 2JKH 2UWL 2UWO 2UWP 2VH0 2VH6 2VVC 2VVU 2VVV 2VWL 2VWM 2VWN 2VWO
• Descriptor: ACTIVATED FACTOR XA HEAVY CHAIN, 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: serine protease, egf-like domain, blood coagulation, gamma-carboxyglutamic acid, hydrolase, polymorphism, glycoprotein, hydroxylation, calcium, zymogen, protease, secreted, factor xa, cleavage on pair of basic residues
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 32423.26

Authors

Roehrig, S.,Straub, A.,Pohlmann, J.,Lampe, T.,Pernerstorfer, J.,Schlemmer, K.,Reinemer, P.,Perzborn, E.,Schaefer, M. (deposition date: 2008-10-24, release date: 2008-11-11, Last modification date: 2021-04-28)

Primary citation

Roehrig, S.,Straub, A.,Pohlmann, J.,Lampe, T.,Pernerstorfer, J.,Schlemmer, K.,Reinemer, P.,Perzborn, E.
Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-2-Oxo-3- [4-(3-Oxomorpholin-4-Yl)Phenyl]-1,3-Oxazolidin-5-Yl}Methyl)Thiophene-2- Carboxamide (Bay 59-7939): An Oral, Direct Factor Xa Inhibitor.
J.Med.Chem., 48:5900-5908, 2005

PubMed Abstract: Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases.

PubMed: 16161994
DOI: 10.1021/JM050101D

Experimental method

X-RAY DIFFRACTION (2.08 Å)