3LPB

Crystal structure of Jak2 complexed with a potent 2,8-diaryl-quinoxaline inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 

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Ligand Structure Quality Assessment 


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


Literature

Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors

Pissot-Soldermann, C., Gerspacher, M., Furet, P., Gaul, C., Holzer, P., McCarthy, C., Radimerski, T., Regnier, C.H., Baffert, F., Drueckes, P., Tavares, G.A., Vangrevelinghe, E., Blasco, F., Ottaviani, G., Ossola, F., Scesa, J., Reetz, J.

(2010) Bioorg Med Chem Lett 20: 2609-2613

  • DOI: https://doi.org/10.1016/j.bmcl.2010.02.056
  • Primary Citation of Related Structures:  
    3LPB

  • PubMed Abstract: 

    We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation.

    • Organizational Affiliation: 

    Novartis Institutes for Biomedical Research, Novartis Pharma AG, WKL-136.4.96, CH-4002 Basel, Switzerland. carole.pissot@novartis.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK2
A, B
295Homo sapiensMutation(s): 0 
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for O60674 (Homo sapiens)
Explore O60674 
Go to UniProtKB:  O60674
PHAROS:  O60674
GTEx:  ENSG00000096968 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60674
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NVB
Query on NVB
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		N-methyl-4-[3-(3,4,5-trimethoxyphenyl)quinoxalin-5-yl]benzenesulfonamide
C24 H23 N3 O5 S
LYSCAOWDVVWGQK-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A, B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
NVB BindingDB:  3LPB IC50: 42 (nM) from 1 assay(s)
PDBBind:  3LPB IC50: 42 (nM) from 1 assay(s)
Binding MOAD:  3LPB IC50: 42 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.39α = 90
b = 112.39β = 90
c = 70.651γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

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: 2010-04-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2023-11-22
    Changes: Data collection