2VV9

CDK2 in complex with an imidazole piperazine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Imidazole Piperazines: Sar and Development of a Potent Class of Cyclin-Dependent Kinase Inhibitors with a Novel Binding Mode.

Finlay, M.R.Acton, D.G.Andrews, D.M.Barker, A.J.Dennis, M.Fisher, E.Graham, M.A.Green, C.P.Heaton, D.W.Karoutchi, G.Loddick, S.A.Morgentin, R.Roberts, A.Tucker, J.A.Weir, H.M.

(2008) Bioorg Med Chem Lett 18: 4442

  • DOI: https://doi.org/10.1016/j.bmcl.2008.06.027
  • Primary Citation of Related Structures:  
    2VV9

  • PubMed Abstract: 

    A piperazine series of cyclin-dependent kinase (CDK) inhibitors have been identified. The compounds exhibit excellent physiochemical properties and a novel binding mode, whereby a bridging interaction via a water molecule with Asp 86 of CDK2, leads to selectivity for the CDK family of enzymes over other kinases. Piperazines 2e and 2i were subsequently shown to inhibit tumour growth when dosed orally in a nude mouse xenograft study. Additional chemical series that exploit this unexpected interaction with Asp 86 are also described.


  • Organizational Affiliation

    Cancer and Infection Research Area, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. ray.finlay@astrazeneca.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CELL DIVISION PROTEIN KINASE 2299Homo sapiensMutation(s): 0 
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
IM9
Query on IM9

Download Ideal Coordinates CCD File 
B [auth A]2-{4-[4-({4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]pyrimidin-2-yl}amino)phenyl]piperazin-1-yl}-2-oxoethanol
C23 H29 N7 O2
PVTKDXZNSUHUMO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IM9 BindingDB:  2VV9 IC50: 17 (nM) from 1 assay(s)
Binding MOAD:  2VV9 IC50: 17 (nM) from 1 assay(s)
PDBBind:  2VV9 IC50: 17 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.252α = 90
b = 71.153β = 90
c = 71.933γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
TRUNCATEdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-05
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2019-04-24
    Changes: Data collection, Derived calculations, Other, Source and taxonomy