3TTJ

Crystal Structure of JNK3 complexed with CC-359, a JNK inhibitor for the prevention of ischemia-reperfusion injury


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury.

Krenitsky, V.P.Delgado, M.Nadolny, L.Sahasrabudhe, K.Ayala, L.Clareen, S.S.Hilgraf, R.Albers, R.Kois, A.Hughes, K.Wright, J.Nowakowski, J.Sudbeck, E.Ghosh, S.Bahmanyar, S.Chamberlain, P.Muir, J.Cathers, B.E.Giegel, D.Xu, L.Celeridad, M.Moghaddam, M.Khatsenko, O.Omholt, P.Katz, J.Pai, S.Fan, R.Tang, Y.Shirley, M.A.Benish, B.Blease, K.Raymon, H.Bhagwat, S.Henderson, I.Cole, A.G.Bennett, B.Satoh, Y.

(2012) Bioorg Med Chem Lett 22: 1427-1432

  • DOI: https://doi.org/10.1016/j.bmcl.2011.12.028
  • Primary Citation of Related Structures:  
    3TTJ

  • PubMed Abstract: 

    In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.


  • Organizational Affiliation

    Celgene Corporation, 4550 Towne Centre Court, San Diego, CA 92121, USA. vplantev@celgene.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 10464Homo sapiensMutation(s): 0 
Gene Names: MAPK10JNK3JNK3APRKM10
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P53779 (Homo sapiens)
Explore P53779 
Go to UniProtKB:  P53779
PHAROS:  P53779
GTEx:  ENSG00000109339 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53779
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
JBI
Query on JBI

Download Ideal Coordinates CCD File 
B [auth A]9-cyclopentyl-N~8~-(2-fluorophenyl)-N~2~-(4-methoxyphenyl)-9H-purine-2,8-diamine
C23 H23 F N6 O
IMFVPVKPQOQCBY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
JBI BindingDB:  3TTJ IC50: min: 210, max: 1100 (nM) from 2 assay(s)
Binding MOAD:  3TTJ IC50: 210 (nM) from 1 assay(s)
PDBBind:  3TTJ IC50: 210 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.173α = 90
b = 70.733β = 90
c = 106.396γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
MOSFLMdata reduction
d*TREKdata reduction
d*TREKdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-01-25
    Type: Initial release
  • Version 1.1: 2012-02-08
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations