3IG7

Novel CDK-5 inhibitors - crystal structure of inhibitor EFP with CDK-2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease.

Helal, C.J.Kang, Z.Lucas, J.C.Gant, T.Ahlijanian, M.K.Schachter, J.B.Richter, K.E.Cook, J.M.Menniti, F.S.Kelly, K.Mente, S.Pandit, J.Hosea, N.

(2009) Bioorg Med Chem Lett 19: 5703-5707

  • DOI: https://doi.org/10.1016/j.bmcl.2009.08.019
  • Primary Citation of Related Structures:  
    3IG7, 3IGG

  • PubMed Abstract: 

    Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.


  • Organizational Affiliation

    Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. chris.j.helal@pfizer.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 
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
EFP
Query on EFP

Download Ideal Coordinates CCD File 
B [auth A]N-{1-[cis-3-(acetylamino)cyclobutyl]-1H-imidazol-4-yl}-2-(4-methoxyphenyl)acetamide
C18 H22 N4 O3
PUVVKKBHOWNLRX-GASCZTMLSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EFP PDBBind:  3IG7 IC50: 63 (nM) from 1 assay(s)
Binding MOAD:  3IG7 IC50: 9 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.343α = 90
b = 70.994β = 90
c = 71.811γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2009-09-08 
  • Deposition Author(s): Pandit, J.

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance