3ULI

Human Cyclin Dependent Kinase 2 (CDK2) bound to azabenzimidazole derivative


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.302 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.238 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKK epsilon kinases.

Wang, T.Block, M.A.Cowen, S.Davies, A.M.Devereaux, E.Gingipalli, L.Johannes, J.Larsen, N.A.Su, Q.Tucker, J.A.Whitston, D.Wu, J.Zhang, H.J.Zinda, M.Chuaqui, C.

(2012) Bioorg Med Chem Lett 22: 2063-2069

  • DOI: https://doi.org/10.1016/j.bmcl.2012.01.018
  • Primary Citation of Related Structures:  
    3ULI

  • PubMed Abstract: 

    The design, synthesis and biological evaluation of a series of azabenzimidazole derivatives as TBK1/IKKε kinase inhibitors are described. Starting from a lead compound 1a, iterative design and SAR exploitation of the scaffold led to analogues with nM enzyme potencies against TBK1/IKKε. These compounds also exhibited excellent cellular activity against TBK1. Further structure-based design to improve selectivity over CDK2 and Aurora B resulted in compounds such as 5b-e. These probe compounds will facilitate study of the complex cancer biology of TBK1 and IKKε.


  • Organizational Affiliation

    Department of Cancer Chemistry, Oncology Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. tao.wang@astrazeneca.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-dependent kinase 2298Homo sapiensMutation(s): 0 
Gene Names: CDK2CDKN2
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
1N3
Query on 1N3

Download Ideal Coordinates CCD File 
B [auth A]1-(aminomethyl)-N-(3-{[6-bromo-2-(4-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-7-yl]amino}propyl)cyclopropanecarboxamide
C21 H25 Br N6 O2
XUELBKVSGYWSKD-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1N3 Binding MOAD:  3ULI IC50: 70 (nM) from 1 assay(s)
PDBBind:  3ULI IC50: 70 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.302 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.238 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.304α = 90
b = 71.352β = 90
c = 71.914γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata 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: 2013-08-14
    Type: Initial release
  • Version 1.1: 2013-09-04
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations