2PR3

Factor XA inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.255 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors

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.

(2007) Chem Biol Drug Des 69: 444-450

  • DOI: https://doi.org/10.1111/j.1747-0285.2007.00520.x
  • Primary Citation of Related Structures:  
    2PR3

  • 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.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
COAGULATION FACTOR X, HEAVY CHAIN234Homo sapiensMutation(s): 0 
Gene Names: F10
EC: 3.4.21.6
UniProt & NIH Common Fund Data Resources
Find proteins for P00742 (Homo sapiens)
Explore P00742 
Go to UniProtKB:  P00742
PHAROS:  P00742
GTEx:  ENSG00000126218 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00742
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
COAGULATION FACTOR X, LIGHT CHAIN51Homo sapiensMutation(s): 0 
Gene Names: F10
EC: 3.4.21.6
UniProt & NIH Common Fund Data Resources
Find proteins for P00742 (Homo sapiens)
Explore P00742 
Go to UniProtKB:  P00742
PHAROS:  P00742
GTEx:  ENSG00000126218 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00742
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
237
Query on 237

Download Ideal Coordinates CCD File 
E [auth A](2R,4R)-N~1~-(4-CHLOROPHENYL)-N~2~-[3-FLUORO-2'-(METHYLSULFONYL)BIPHENYL-4-YL]-4-METHOXYPYRROLIDINE-1,2-DICARBOXAMIDE
C26 H25 Cl F N3 O5 S
QBTQRXKLWHEJQY-AUSIDOKSSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
237 BindingDB:  2PR3 IC50: min: 0.16, max: 1.7 (nM) from 2 assay(s)
Binding MOAD:  2PR3 IC50: 0.16 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.255 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.485α = 90
b = 72.354β = 90
c = 77.88γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-08-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.2: 2017-10-18
    Changes: Refinement description