7NEU

Inhibitor Complex with Thrombin Activatable Fibrinolysis Inhibitor (TAFIa)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa).

Schaffner, A.P.Sansilvestri-Morel, P.Despaux, N.Ruano, E.Persigand, T.Rupin, A.Mennecier, P.Vallez, M.O.Raimbaud, E.Desos, P.Gloanec, P.

(2021) J Med Chem 64: 3897-3910

  • DOI: 10.1021/acs.jmedchem.0c02072
  • Primary Citation of Related Structures:  
    7NEE, 7NEU

  • PubMed Abstract: 
  • Selective and potent inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) have the potential to increase endogenous and therapeutic fibrinolysis and to behave like profibrinolytic agents without the risk of major hemorrhage, since they do not interfere either with platelet activation or with coagulation during blood hemostasis ...

    Selective and potent inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) have the potential to increase endogenous and therapeutic fibrinolysis and to behave like profibrinolytic agents without the risk of major hemorrhage, since they do not interfere either with platelet activation or with coagulation during blood hemostasis. Therefore, TAFIa inhibitors could be used in at-risk patients for the treatment, prevention, and secondary prevention of stroke, venous thrombosis, and pulmonary embolisms. In this paper, we describe the design, the structure-activity relationship (SAR), and the synthesis of novel, potent, and selective phosphinanes and azaphosphinanes as TAFIa inhibitors. Several highly active azaphosphinanes display attractive properties suitable for further in vivo efficacy studies in thrombosis models.


    Organizational Affiliation

    Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, et 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Carboxypeptidase B2 A400Homo sapiensMutation(s): 0 
Gene Names: CPB2
EC: 3.4.17.20
Find proteins for Q96IY4 (Homo sapiens)
Explore Q96IY4 
Go to UniProtKB:  Q96IY4
NIH Common Fund Data Resources
PHAROS:  Q96IY4
Protein Feature View
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
U9K
Query on U9K

Download Ideal Coordinates CCD File 
A
(1R,3S)-3-(4-ammoniobutyl)-1-(4-fluoro-2-(1-methyl-1H-imidazol-5-yl)benzyl)-1,4-azaphosphinan-1-ium-3-carboxylate 4,4-dioxide
C20 H30 F N4 O4 P
ZBWZIBATIOSFOY-FQEVSTJZSA-P
 Ligand Interaction
NAG
Query on NAG

Download Ideal Coordinates CCD File 
A
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
ZN
Query on ZN

Download Ideal Coordinates CCD File 
A
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
EDO
Query on EDO

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A
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
 Ligand Interaction
CL
Query on CL

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A
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
 Ligand Interaction
NA
Query on NA

Download Ideal Coordinates CCD File 
A
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.201 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.42α = 90
b = 157.35β = 90
c = 64.08γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2021-04-07
    Type: Initial release
  • Version 1.1: 2021-04-21
    Changes: Database references