4QD6

ITK kinase domain in complex with inhibitor compound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.212 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Design, synthesis and structure-activity relationships of a novel class of sulfonylpyridine inhibitors of Interleukin-2 inducible T-cell kinase (ITK).

Trani, G.Barker, J.J.Bromidge, S.M.Brookfield, F.A.Burch, J.D.Chen, Y.Eigenbrot, C.Heifetz, A.Ismaili, M.H.Johnson, A.Krulle, T.M.MacKinnon, C.H.Maghames, R.McEwan, P.A.Montalbetti, C.A.Ortwine, D.F.Perez-Fuertes, Y.Vaidya, D.G.Wang, X.Zarrin, A.A.Pei, Z.

(2014) Bioorg Med Chem Lett 24: 5818-5823

  • DOI: https://doi.org/10.1016/j.bmcl.2014.10.020
  • Primary Citation of Related Structures:  
    4QD6

  • PubMed Abstract: 

    Starting from benzylpyrimidine 2, molecular modeling and X-ray crystallography were used to design highly potent inhibitors of Interleukin-2 inducible T-cell kinase (ITK). Sulfonylpyridine 4i showed sub-nanomolar affinity against ITK, was selective versus Lck and its activity in the Jurkat cell-based assay was greatly improved over 2.


  • Organizational Affiliation

    Discovery Chemistry, Evotec UK Ltd, 114 Innovation Drive, Milton Park, Abingdon, OX14 4RZ, UK. Electronic address: Giancarlo.Trani@evotec.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase ITK/TSK
A, B
266Homo sapiensMutation(s): 1 
Gene Names: ITKEMTLYK
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for Q08881 (Homo sapiens)
Explore Q08881 
Go to UniProtKB:  Q08881
PHAROS:  Q08881
GTEx:  ENSG00000113263 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ08881
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
30T
Query on 30T

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
trans-4-({6-[(5-phenyl-1H-pyrazol-3-yl)amino]-4-(phenylsulfonyl)pyridin-2-yl}amino)cyclohexanol
C26 H27 N5 O3 S
YIGXUZJWVOKKIO-MXVIHJGJSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
30T Binding MOAD:  4QD6 Ki: 2.3 (nM) from 1 assay(s)
BindingDB:  4QD6 Ki: 2.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.212 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.06α = 90
b = 94.32β = 90
c = 156.34γ = 90
Software Package:
Software NamePurpose
GDAdata collection
PHASERphasing
REFMACrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-01-14
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references, Derived calculations