Summary
PDB 2W26 deposited: 2008-10-24 modified: 2012-06-27
Title Fator Xa in complex with BAY59-7939
Authors Lampe, T., Pernerstorfer, J., Perzborn, E., Pohlmann, J., Reinemer, P., Roehrig, S., Schlemmer, K., Straub, A.
Method X-RAY DIFFRACTION
Structure factors resolution 2.08 rfactor 0.2198 rfree 0.2591
DPI 0.51 theoretical min: 0.23
Citations

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.

J.Med.Chem. 2005 Sep; 48(19):5900- doi:10.1021/JM050101D

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1140410
PubMed 16161994 JMCMAR
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2W26/1 2W26 1 dimer 0 2 3 2080