4RX9

SYK Catalytic Domain Complexed with a Potent Pyrimidine Inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Discovery and profiling of a selective and efficacious syk inhibitor.

Thoma, G., Smith, A.B., van Eis, M.J., Vangrevelinghe, E., Blanz, J., Aichholz, R., Littlewood-Evans, A., Lee, C.C., Liu, H., Zerwes, H.G.

(2015) J Med Chem 58: 1950-1963

  • DOI: https://doi.org/10.1021/jm5018863
  • Primary Citation of Related Structures:  
    4RX7, 4RX8, 4RX9

  • PubMed Abstract: 

    We describe the discovery of selective and potent Syk inhibitor 11, which exhibited favorable PK profiles in rat and dog and was found to be active in a collagen-induced arthritis model in rats. Compound 11 was selected for further profiling, but, unfortunately, in GLP toxicological studies it showed liver findings in rat and dog. Nevertheless, 11 could become a valuable tool compound to investigate the rich biology of Syk in vitro and in vivo.

    • Organizational Affiliation: 

    Global Discovery Chemistry, ‡Analytical Sciences & Imaging, §Autoimmunity, Transplantation and Inflammation Research, Novartis Institutes for Biomedical Research , 4056 Basel, Switzerland.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase SYK290Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3YT
Query on 3YT
Download Ideal Coordinates CCD File 
C [auth A]2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-{[3-(2H-1,2,3-triazol-2-yl)phenyl]amino}pyrimidine-5-carboxamide
C19 H23 N9 O
TXGKRVFSSHPBAJ-JKSUJKDBSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
B [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3YT BindingDB:  4RX9 IC50: min: 1, max: 952 (nM) from 9 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.978α = 90
b = 85.126β = 90
c = 89.776γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
BUSTERrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2015-03-18 
    • Deposition Author(s): Lee, C.C.

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-18
    Type: Initial release
  • Version 1.1: 2017-11-22
    Changes: Refinement description
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations