2Y7X

The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

The Discovery of Potent and Long-Acting Oral Factor Xa Inhibitors with Tetrahydroisoquinoline and Benzazepine P4 Motifs.

Watson, N.S.Adams, C.Belton, D.Brown, D.Burns-Kurtis, C.L.Chaudry, L.Chan, C.Convery, M.A.Davies, D.E.Exall, A.M.Harling, J.D.Irvine, S.Irving, W.R.Kleanthous, S.Mclay, I.M.Pateman, A.J.Patikis, A.N.Roethke, T.J.Senger, S.Stelman, G.J.Toomey, J.R.West, R.I.Whittaker, C.Zhou, P.Young, R.J.

(2011) Bioorg Med Chem Lett 21: 1588

  • DOI: https://doi.org/10.1016/j.bmcl.2011.01.129
  • Primary Citation of Related Structures:  
    2Y7X

  • PubMed Abstract: 

    The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies.


  • Organizational Affiliation

    GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ACTIVATED FACTOR XA HEAVY CHAIN254Homo 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
FACTOR X LIGHT CHAIN134Homo 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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MZA
Query on MZA

Download Ideal Coordinates CCD File 
C [auth A]6-CHLORO-N-[(3S)-1-(5-FLUORO-1,2,3,4-TETRAHYDROISOQUINOLIN-6-YL)-2-OXO-PYRROLIDIN-3-YL]NAPHTHALENE-2-SULFONAMIDE
C23 H21 Cl F N3 O3 S
BJOZEZZETKKCMQ-FQEVSTJZSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
D [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MZA PDBBind:  2Y7X Ki: 1.3 (nM) from 1 assay(s)
BindingDB:  2Y7X Ki: 1.3 (nM) from 1 assay(s)
Binding MOAD:  2Y7X Ki: 1.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.859α = 90
b = 71.599β = 90
c = 78.279γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2011-03-16
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-06-28
    Changes: Data collection