1WU1

Factor Xa in complex with the inhibitor 4-[(5-chloroindol-2-yl)sulfonyl]-2-(2-methylpropyl)-1-[[5-(pyridin-4-yl) pyrimidin-2-yl]carbonyl]piperazine

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history. 


Literature

Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites

Komoriya, S., Haginoya, N., Kobayashi, S., Nagata, T., Mochizuki, A., Suzuki, M., Yoshino, T., Horino, H., Nagahara, T., Suzuki, M., Isobe, Y., Furugoori, T.

(2005) Bioorg Med Chem 13: 3927-3954

  • DOI: https://doi.org/10.1016/j.bmc.2005.04.006
  • Primary Citation of Related Structures:  
    1WU1, 2D1J

  • PubMed Abstract: 

    Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1mg/kg of compound 75b.

    • Organizational Affiliation: 

    Tokyo R&D Center, Daiichi Pharmaceutical Co. Ltd, 16-13 Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. komor0ni@daiichipharm.co.jp


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor X, heavy chain233Homo sapiensMutation(s): 0 
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
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor X, light chain95Homo sapiensMutation(s): 0 
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
D91
Query on D91
Download Ideal Coordinates CCD File 
E [auth A]5-CHLORO-2-({3-ISOBUTYL-4-[(5-PYRIDIN-4-YLPYRIMIDIN-2-YL)CARBONYL]PIPERAZIN-1-YL}SULFONYL)-1H-INDOLE
C26 H27 Cl N6 O3 S
JUUFKVAFKAKWRV-JOCHJYFZSA-N
CA
Query on CA
Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]		CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
BHD
Query on BHD
B
L-PEPTIDE LINKINGC4 H7 N O5ASP
Binding Affinity Annotations 
IDSourceBinding Affinity
D91 PDBBind:  1WU1 IC50: 18 (nM) from 1 assay(s)
Binding MOAD:  1WU1 IC50: 18 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.569α = 90
b = 72.487β = 90
c = 79.02γ = 90
Software Package:
Software NamePurpose
d*TREKdata scaling
d*TREKdata reduction
REFMACrefinement

Structure Validation

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View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2005-11-29 
    • Deposition Author(s): Suzuki, M.

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-29
    Type: Initial release
  • Version 1.1: 2008-04-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2012-06-20
    Changes: Non-polymer description
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description