1R78

CDK2 complex with a 4-alkynyl oxindole inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

A new series of potent oxindole inhibitors of CDK2

Luk, K.-C.Simcox, M.E.Schutt, A.Rowan, K.Thompson, T.Chen, Y.Kammlott, U.DePinto, W.Dunten, P.Dermatakis, A.

(2004) Bioorg Med Chem Lett 14: 913-917

  • DOI: https://doi.org/10.1016/j.bmcl.2003.12.009
  • Primary Citation of Related Structures:  
    1R78

  • PubMed Abstract: 

    A novel series of oxindole-type inhibitors of CDK2 that have heteroatom substituted alkynyl moieties at their C-4 position is described. These novel 4-alkynyl-substituted inhibitors have superior potency relative to their parent compound in free enzyme and in cell based assays. The crystal structure of CDK2 in complex with one of these analogues was determined and gives insight to their increased potency. The biochemical evaluation of a representative derivative is also described.


  • Organizational Affiliation

    Hoffmann-La Roche Inc., 340 Kingsland St., Nutley, NJ 07110-1199, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 2298Homo sapiensMutation(s): 0 
Gene Names: CDK2
EC: 2.7.1
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
FMD
Query on FMD

Download Ideal Coordinates CCD File 
B [auth A]4-((3R,4S,5R)-4-AMINO-3,5-DIHYDROXY-HEX-1-YNYL)-5-FLUORO-3-[1-(3-METHOXY-1H-PYRROL-2-YL)-METH-(Z)-YLIDENE]-1,3-DIHYDRO-INDOL-2-ONE
C20 H20 F N3 O4
RAKYKJWUUUKCCW-MPLBGYFPSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FMD PDBBind:  1R78 IC50: 3 (nM) from 1 assay(s)
Binding MOAD:  1R78 IC50: 3 (nM) from 1 assay(s)
BindingDB:  1R78 IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.220 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.88α = 90
b = 71.962β = 90
c = 72.779γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-01-20
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations