2G00

Factor Xa in complex with the inhibitor 3-(6-(2'-((dimethylamino)methyl)-4-biphenylyl)-7-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl)benzamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.269 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties.

Pinto, D.J.Galemmo, R.A.Quan, M.L.Orwat, M.J.Clark, C.Li, R.Wells, B.Woerner, F.Alexander, R.S.Rossi, K.A.Smallwood, A.Wong, P.C.Luettgen, J.M.Rendina, A.R.Knabb, R.M.He, K.Wexler, R.R.Lam, P.Y.

(2006) Bioorg Med Chem Lett 16: 5584-5589

  • DOI: https://doi.org/10.1016/j.bmcl.2006.08.027
  • Primary Citation of Related Structures:  
    2G00

  • PubMed Abstract: 

    The bicyclic dihydropyrazolopyridinone scaffold allowed for incorporation of multiple P1 moieties with subnanomolar binding affinities for blood coagulation factor Xa. The compound 3-[6-(2'-dimethylaminomethyl-biphenyl-4-yl)-7-oxo-3-trifluoro-methyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridine-l-yl]-benzamide 6d shows good fXa potency, selectivity, in vivo efficacy and oral bioavailability. Compound 6d was selected for further pre-clinical evaluations.


  • Organizational Affiliation

    Discovery Chemistry Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. Donald.Pinto@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor X234Homo 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 XB [auth L]52Homo 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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4QC
Query on 4QC

Download Ideal Coordinates CCD File 
C [auth A]3-[6-{2'-[(DIMETHYLAMINO)METHYL]BIPHENYL-4-YL}-7-OXO-3-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3,4-C]PYRIDIN-1-YL]BENZAMIDE
C29 H26 F3 N5 O2
PKGPGSWPKRHPKB-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4QC Binding MOAD:  2G00 Ki: 0.18 (nM) from 1 assay(s)
PDBBind:  2G00 Ki: 0.18 (nM) from 1 assay(s)
BindingDB:  2G00 Ki: 0.18 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.269 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.6α = 90
b = 72.4β = 90
c = 78.9γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
EPMRphasing
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-03
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Advisory, Refinement description