5WB6

FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(11S)-11-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-6-fluoro-2-oxo-1,3,4,10,11,13-hexahydro-2H-5,9:15,12-di(azeno)-1,13-benzodiazacycloheptadecin-18-yl]carbamate

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Macrocyclic factor XIa inhibitors.

Wang, C., Corte, J.R., Rossi, K.A., Bozarth, J.M., Wu, Y., Sheriff, S., Myers, J.E., Luettgen, J.M., Seiffert, D.A., Wexler, R.R., Quan, M.L.

(2017) Bioorg Med Chem Lett 27: 4056-4060

  • DOI: https://doi.org/10.1016/j.bmcl.2017.07.048
  • Primary Citation of Related Structures:  
    5WB6

  • PubMed Abstract: 

    A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, and good potency in the activated partial thromboplastin time (aPTT) clotting assay.

    • Organizational Affiliation: 

    Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540 United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor XI244Homo sapiensMutation(s): 2 
Gene Names: F11
EC: 3.4.21.27
UniProt & NIH Common Fund Data Resources
Find proteins for P03951 (Homo sapiens)
Explore P03951 
Go to UniProtKB:  P03951
PHAROS:  P03951
GTEx:  ENSG00000088926 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03951
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
9ZM
Query on 9ZM
Download Ideal Coordinates CCD File 
B [auth A]methyl [(11S)-11-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-6-fluoro-2-oxo-1,3,4,10,11,13-hexahydro-2H-5,9:15,12-di(azeno)-1,13-benzodiazacycloheptadecin-18-yl]carbamate
C31 H26 Cl F N10 O4
RMPNNJSYICOFTF-PRQZJMEUSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
C [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
EDO
Query on EDO
Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
9ZM BindingDB:  5WB6 Ki: 0.02 (nM) from 1 assay(s)
Binding MOAD:  5WB6 Ki: 0.02 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.6α = 90
b = 78.6β = 90
c = 106γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2017-08-02 
    • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-02
    Type: Initial release
  • Version 1.1: 2017-08-23
    Changes: Database references
  • Version 1.2: 2017-08-30
    Changes: Database references
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description