2EI6

FACTOR XA IN COMPLEX WITH THE INHIBITOR (-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history. 


Literature

Cycloalkanediamine derivatives as novel blood coagulation factor Xa inhibitors.

Nagata, T., Yoshino, T., Haginoya, N., Yoshikawa, K., Isobe, Y., Furugohri, T., Kanno, H.

(2007) Bioorg Med Chem Lett 17: 4683-4688

  • DOI: https://doi.org/10.1016/j.bmcl.2007.05.068
  • Primary Citation of Related Structures:  
    2EI6

  • PubMed Abstract: 

    This paper describes the synthesis of orally available potent fXa inhibitors 2 and 3 by modification of the piperazine part of lead compound 1. Carbonyl derivative 3 showed potent fXa activity but not sulfonyl derivative 2. Among the compounds synthesized, cyclohexane derivatives 3g and 3h and cycloheptane derivative 3j had potent anticoagulant activity as well as anti-fXa activity. Synthetic study of the optical isomers of 3g demonstrated that (-)-3g had more potent activity.

    • Organizational Affiliation: 

    Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan. nagatso1@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 chain54Homo 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
D92
Query on D92
Download Ideal Coordinates CCD File 
E [auth A]N-((1R,2S)-2-(5-CHLORO-1H-INDOLE-2-CARBOXAMIDO)CYCLOHEXYL)-5-METHYL-4,5,6,7-TETRAHYDROTHIAZOLO[5,4-C]PYRIDINE-2-CARBOXAMIDE
C23 H26 Cl N5 O2 S
ARPFWVKYXJZULB-DLBZAZTESA-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
D92 BindingDB:  2EI6 IC50: min: 16, max: 41 (nM) from 2 assay(s)
PDBBind:  2EI6 IC50: 41 (nM) from 1 assay(s)
Binding MOAD:  2EI6 IC50: 16 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.805α = 90
b = 72.971β = 90
c = 79.552γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
d*TREKdata reduction
d*TREKdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2008-03-18 
    • Deposition Author(s): Suzuki, M.

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description