2PR3

Factor XA inhibitor

Summary for 2PR3

• Entry DOI: 10.2210/pdb2pr3/pdb
• Related: 2G0M 2G21 2PHB
• Descriptor: COAGULATION FACTOR X, HEAVY CHAIN, COAGULATION FACTOR X, LIGHT CHAIN, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: fxa coagulation factor inhibitor, blood clotting
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 32533.32

Authors

Zhang, E.,Kohrt, J.T.,Bigge, C.F.,Finzel, B.C. (deposition date: 2007-05-03, release date: 2007-08-14, Last modification date: 2024-11-20)

Primary citation

Van Huis, C.A.,Bigge, C.F.,Casimiro-Garcia, A.,Cody, W.L.,Dudley, D.A.,Filipski, K.J.,Heemstra, R.J.,Kohrt, J.T.,Narasimhan, L.S.,Schaum, R.P.,Zhang, E.,Bryant, J.W.,Haarer, S.,Janiczek, N.,Leadley, R.J.,McClanahan, T.,Thomas Peterson, J.,Welch, K.M.,Edmunds, J.J.
Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors
Chem.Biol.Drug Des., 69:444-450, 2007

PubMed Abstract: A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor Xa inhibitors using structure-based drug design. This series consisted of a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) = 0.38 nM), which was shown to be efficacious in a canine electrolytic model of thrombosis with minimal bleeding.

PubMed: 17581239
DOI: 10.1111/j.1747-0285.2007.00520.x

Experimental method

X-RAY DIFFRACTION (1.5 Å)