4AWI

Human Jnk1alpha kinase with 4-phenyl-7-azaindole IKK2 inhibitor.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.91 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

4-Phenyl-7-Azaindoles as Potent, Selective and Bioavailable Ikk2 Inhibitors Demonstrating Good in Vivo Efficacy.

Liddle, J., Bamborough, P., Barker, M.D., Campos, S., Chung, C., Cousins, R.P.C., Faulder, P., Heathcote, M.L., Hobbs, H., Holmes, D.S., Ioannou, C., Ramirez-Molina, C., Morse, M.A., Osborn, R., Payne, J.J., Pritchard, J.M., Rumsey, W.L., Tape, D.T., Vicentini, G., Whitworth, C., Williamson, R.A.

(2012) Bioorg Med Chem Lett 22: 5222

  • DOI: https://doi.org/10.1016/j.bmcl.2012.06.065
  • Primary Citation of Related Structures:  
    4AWI

  • PubMed Abstract: 

    The lead optimization of a series of potent azaindole IKK2 inhibitors is described. Optimization of the human whole blood activity and selectivity over IKK1 in parallel led to the discovery of 16, a potent and selective IKK2 inhibitor showing good efficacy in a rat model of neutrophil activation.

    • Organizational Affiliation: 

    GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. john.2.liddle@gsk.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MITOGEN-ACTIVATED PROTEIN KINASE 8369Homo sapiensMutation(s): 0 
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P45983 (Homo sapiens)
Explore P45983 
Go to UniProtKB:  P45983
PHAROS:  P45983
GTEx:  ENSG00000107643 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45983
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
AQ2
Query on AQ2
Download Ideal Coordinates CCD File 
B [auth A]N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4-[2-(1-methylethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]benzenesulfonamide
C21 H25 N3 O4 S2
QBYYCHRRPPTEBG-UHFFFAOYSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]		SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
AQ2 Binding MOAD:  4AWI IC50: 1000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.91 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.438α = 90
b = 72.747β = 90
c = 110.155γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata 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: 2013-05-01
    Type: Initial release
  • Version 1.1: 2014-07-30
    Changes: Database references