5T68

Crystal structure of Syk catalytic domain in complex with a furo[3,2-d]pyrimidine

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.93 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.188 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history. 


Literature

Synthesis and optimization of furano[3,2-d]pyrimidines as selective spleen tyrosine kinase (Syk) inhibitors.

Hoemann, M., Wilson, N., Argiriadi, M., Banach, D., Burchat, A., Calderwood, D., Clapham, B., Cox, P., Duignan, D.B., Konopacki, D., Somal, G., Vasudevan, A.

(2016) Bioorg Med Chem Lett 26: 5562-5567

  • DOI: https://doi.org/10.1016/j.bmcl.2016.09.077
  • Primary Citation of Related Structures:  
    5T68

  • PubMed Abstract: 

    A series of furano[3,2-d]pyrimidine Syk inhibitors were synthesized and optimized for their enzyme potency and selectivity versus other kinases. In addition, ADME properties were assessed and compounds were prepared with optimized profiles for in vivo experiments. Compound 23 was identified as having acceptable pharmacokinetic properties and demonstrated efficacy in a rat collagen induced arthritis model.

    • Organizational Affiliation: 

    AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase SYK
A, B
291Homo sapiensMutation(s): 0 
Gene Names: SYK
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P43405 (Homo sapiens)
Explore P43405 
Go to UniProtKB:  P43405
PHAROS:  P43405
GTEx:  ENSG00000165025 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP43405
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
77V
Query on 77V
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		N~4~-cyclopropyl-N~2~-(3-methyl-1H-indazol-6-yl)furo[3,2-d]pyrimidine-2,4-diamine
C17 H16 N6 O
MDWXVGCLSBQVMP-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
77V BindingDB:  5T68 IC50: min: 23, max: 24 (nM) from 2 assay(s)
EC50: 34 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.93 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.188 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.605α = 90.16
b = 40.03β = 89.98
c = 84.046γ = 99.8
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-10-26
    Type: Initial release
  • Version 1.1: 2016-11-16
    Changes: Database references
  • Version 1.2: 2016-12-28
    Changes: Database references
  • Version 1.3: 2017-09-27
    Changes: Data collection
  • Version 1.4: 2023-10-04
    Changes: Data collection, Database references, Refinement description