2PVM

Structure-Based Design of Pyrazolo[1,5-a][1,3,5]triazine Derivatives as Potent Inhibitors of Protein Kinase CK2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2.

Nie, Z.Perretta, C.Erickson, P.Margosiak, S.Almassy, R.Lu, J.Averill, A.Yager, K.M.Chu, S.

(2007) Bioorg Med Chem Lett 17: 4191-4195

  • DOI: https://doi.org/10.1016/j.bmcl.2007.05.041
  • Primary Citation of Related Structures:  
    2PVH, 2PVJ, 2PVK, 2PVL, 2PVM, 2PVN

  • PubMed Abstract: 

    The structure-based design, synthesis, and anticancer activity of novel inhibitors of protein kinase CK2 are described. Using pyrazolo[1,5-a][1,3,5]triazine as the core scaffold, a structure-guided series of modifications provided pM inhibitors with microM-level cytotoxic activity in cell-based assays with prostate and colon cancer cell lines.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Polaris Pharmaceuticals Inc., San Diego, CA 92121, USA. zhe.nie@takedasd.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha352Zea maysMutation(s): 1 
Gene Names: ACK2
EC: 2.7.11.1
UniProt
Find proteins for P28523 (Zea mays)
Explore P28523 
Go to UniProtKB:  P28523
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28523
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P29
Query on P29

Download Ideal Coordinates CCD File 
B [auth A]4-(2-(1H-IMIDAZOL-4-YL)ETHYLAMINO)-2-(PHENYLAMINO)PYRAZOLO[1,5-A][1,3,5]TRIAZINE-8-CARBONITRILE
C17 H15 N9
IWUUKHQIKFHWIW-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
P29 PDBBind:  2PVM Ki: 360 (nM) from 1 assay(s)
Binding MOAD:  2PVM Ki: 360 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.188 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.638α = 90
b = 60.145β = 102.901
c = 44.984γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
DENZOdata reduction
CNXphasing
CNXrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-05-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-08-30
    Changes: Data collection, Refinement description
  • Version 1.4: 2023-11-15
    Changes: Data collection