6C0S

Factor XIA in complex with the inhibitor methyl (4-{6-[(1S)-2-[(3R)-1-acetylpiperidin-3-yl]-1-({(2E)-3-[5-chloro-2- (1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)ethyl]-3-chloropyridazin-4-yl}phenyl) carbamate

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 

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Literature

Pyridazine and pyridazinone derivatives as potent and selective factor XIa inhibitors.

Hu, Z., Wang, C., Han, W., 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.

(2018) Bioorg Med Chem Lett 28: 987-992

  • DOI: https://doi.org/10.1016/j.bmcl.2018.02.049
  • Primary Citation of Related Structures:  
    6C0S

  • PubMed Abstract: 

    Pyridazine and pyridazinone derivatives were designed and synthesized as coagulation factor XIa inhibitors. Potent and selective inhibitors with single digit nanomolar affinity for factor XIa were discovered. Selected inhibitors demonstrated moderate oral bioavailability.

    • Organizational Affiliation: 

    Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States. Electronic address: zilun.hu@bms.com.


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
EEJ
Query on EEJ
Download Ideal Coordinates CCD File 
B [auth A]methyl (4-{6-[(1S)-2-[(3R)-1-acetylpiperidin-3-yl]-1-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)ethyl]-3-chloropyridazin-4-yl}phenyl)carbamate
C31 H31 Cl2 N9 O4
QCCGVMDYTWPPFU-BONIYOLGSA-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]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EEJ Binding MOAD:  6C0S Ki: 89 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.9α = 90
b = 78.9β = 90
c = 107γ = 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 


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Entry History 

Deposition Data

  • Released Date: 2018-03-07 
    • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2018-03-07
    Type: Initial release
  • Version 1.1: 2018-03-14
    Changes: Database references
  • Version 1.2: 2018-03-21
    Changes: Database references
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description