2Q1J

The discovery of glycine and related amino acid-based factor xa inhibitors

Summary for 2Q1J

• Entry DOI: 10.2210/pdb2q1j/pdb
• Descriptor: Activated factor Xa heavy chain (EC 3.4.21.6), Factor X light chain (EC 3.4.21.6), CALCIUM ION, ... (5 entities in total)
• Functional Keywords: coagulation fxa, blood coagulation, calcium, cleavage on pair of basic residues, egf-like domain, gamma-carboxyglutamic acid, glycoprotein, hydrolase, hydroxylation, polymorphism, protease, serine protease, zymogen
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 32505.30

Authors

Kohrt, J.T.,Filipski, K.J.,Cody, W.L.,Bigge, C.F.,Zhang, E.,Finzel, B.C. (deposition date: 2007-05-24, release date: 2007-08-14, Last modification date: 2024-10-30)

Primary citation

Kohrt, J.T.,Filipski, K.J.,Cody, W.L.,Bigge, C.F.,La, F.,Welch, K.,Dahring, T.,Bryant, J.W.,Leonard, D.,Bolton, G.,Narasimhan, L.,Zhang, E.,Peterson, J.T.,Haarer, S.,Sahasrabudhe, V.,Janiczek, N.,Desiraju, S.,Hena, M.,Fiakpui, C.,Saraswat, N.,Sharma, R.,Sun, S.,Maiti, S.N.,Leadley, R.,Edmunds, J.J.
The Discovery of Glycine and Related Amino Acid-Based Factor Xa Inhibitors
BIOORG.MED.CHEM., 14:4379-4392, 2006

PubMed Abstract: Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability.

PubMed: 16529937
DOI: 10.1016/j.bmc.2006.02.040

Experimental method

X-RAY DIFFRACTION (1.9 Å)