3EZR

CDK-2 with indazole inhibitor 17 bound at its active site


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: Design and synthesis of a potent and isoform selective PKC-zeta inhibitor

Trujillo, J.I.Kiefer, J.R.Huang, W.Thorarensen, A.Xing, L.Caspers, N.L.Day, J.E.Mathis, K.J.Kretzmer, K.K.Reitz, B.A.Weinberg, R.A.Stegeman, R.A.Wrightstone, A.Christine, L.Compton, R.Li, X.

(2009) Bioorg Med Chem Lett 19: 908-911

  • DOI: https://doi.org/10.1016/j.bmcl.2008.11.105
  • Primary Citation of Related Structures:  
    3EZR, 3EZV, 3F5X

  • PubMed Abstract: 

    The inhibition of PKC-zeta has been proposed to be a potential drug target for immune and inflammatory diseases. A series of 2-(6-phenyl-1H indazol-3-yl)-1H-benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to afford potent and selective inhibitors of protein kinase c-zeta (PKC-zeta). The determination of the crystal structures of key inhibitor:CDK-2 complexes informed the design and analysis of the series. The most selective and potent analog was identified by variation of the aryl substituent at the 6-position of the indazole template to give a 4-NH(2) derivative. The analog displays good selectivity over other PKC isoforms (alpha, betaII, gamma, delta, epsilon, mu, theta, eta and iota/lambda) and CDK-2, however it displays marginal selectivity against a panel of other kinases (37 profiled).


  • Organizational Affiliation

    Department of Medicinal Chemistry, Pfizer Global Research and Development, 700 Chesterfield Pkwy, AA236, Chesterfield, MO 63017, USA. john.i.trujillo@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 2300Homo sapiensMutation(s): 0 
Gene Names: CDK2
EC: 2.7.11.22
UniProt & NIH Common Fund Data Resources
Find proteins for P24941 (Homo sapiens)
Explore P24941 
Go to UniProtKB:  P24941
PHAROS:  P24941
GTEx:  ENSG00000123374 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP24941
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EZR
Query on EZR

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
3-methoxy-4-{3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl}aniline
C26 H27 N7 O
XONAFDRMWJEXGF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EZR BindingDB:  3EZR IC50: 1.00e+4 (nM) from 1 assay(s)
PDBBind:  3EZR IC50: 1.00e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.763α = 90
b = 72.081β = 90
c = 72.392γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations, Structure summary