5CXZ

SYK catalytic domain complexed with naphthyridine inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 

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Ligand Structure Quality Assessment 


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


Literature

Orally bioavailable Syk inhibitors with activity in a rat PK/PD model.

Thoma, G., Veenstra, S., Strang, R., Blanz, J., Vangrevelinghe, E., Berghausen, J., Lee, C.C., Zerwes, H.G.

(2015) Bioorg Med Chem Lett 25: 4642-4647

  • DOI: https://doi.org/10.1016/j.bmcl.2015.08.037
  • Primary Citation of Related Structures:  
    5CXH, 5CXZ, 5CY3

  • PubMed Abstract: 

    Design and optimization of benzo- and pyrido-thiazoles/isothiazoles are reported leading to the discovery of the potent, orally bioavailable Syk inhibitor 5, which was found to be active in a rat PK/PD model. Compound 5 showed acceptable overall kinase selectivity. However, in addition to Syk it also inhibited Aurora kinase in enzymatic and cellular settings leading to findings in the micronucleus assay. As a consequence, compound 5 was not further pursued.

    • Organizational Affiliation: 

    Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland. Electronic address: gebhard.thoma@novartis.com.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase SYK289Homo sapiensMutation(s): 1 
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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
55U
Query on 55U
Download Ideal Coordinates CCD File 
D [auth A]N-{7-[4-(dimethylamino)phenyl]-1,6-naphthyridin-5-yl}propane-1,3-diamine
C19 H23 N5
RIWJHDIYQSQOAT-UHFFFAOYSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
B [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CL
Query on CL
Download Ideal Coordinates CCD File 
C [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
55U Binding MOAD:  5CXZ IC50: 552 (nM) from 1 assay(s)
BindingDB:  5CXZ IC50: min: 34, max: 951 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.08α = 90
b = 87.98β = 90
c = 88.5γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
REFMACphasing

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: 2015-09-16
    Type: Initial release
  • Version 1.1: 2015-10-14
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Database references, Derived calculations, Refinement description
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references