3EJ1

CDK2/CyclinA complexed with a pyrazolopyridazine inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.22 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors.

Stevens, K.L., Reno, M.J., Alberti, J.B., Price, D.J., Kane-Carson, L.S., Knick, V.B., Shewchuk, L.M., Hassell, A.M., Veal, J.M., Davis, S.T., Griffin, R.J., Peel, M.R.

(2008) Bioorg Med Chem Lett 18: 5758-5762

  • DOI: https://doi.org/10.1016/j.bmcl.2008.09.069
  • Primary Citation of Related Structures:  
    3EID, 3EJ1

  • PubMed Abstract: 

    A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3beta.

    • Organizational Affiliation: 

    Department of Oncology, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. Kirk.L.Stevens@gsk.com


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 2
A, C
298Homo 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
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  • Reference Sequence
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-A2
B, D
260Homo sapiensMutation(s): 0 
Gene Names: CCNA2, CCN1, CCNA
UniProt & NIH Common Fund Data Resources
Find proteins for P20248 (Homo sapiens)
Explore P20248 
Go to UniProtKB:  P20248
PHAROS:  P20248
GTEx:  ENSG00000145386 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20248
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5BP
Query on 5BP
Download Ideal Coordinates CCD File 
E [auth A],
F [auth C]		N-cyclopropyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine
C13 H12 N6
CAGHIASAHLPQMS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5BP BindingDB:  3EJ1 IC50: 120 (nM) from 1 assay(s)
PDBBind:  3EJ1 IC50: 120 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.22 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: P 62 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 183.776α = 90
b = 183.776β = 90
c = 214.045γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2019-07-24
    Changes: Data collection, Refinement description
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description