4J52

Crystal structure of PLK1 in complex with a pyrimidodiazepinone inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


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


Literature

Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1).

Nie, Z., Feher, V., Natala, S., McBride, C., Kiryanov, A., Jones, B., Lam, B., Liu, Y., Kaldor, S., Stafford, J., Hikami, K., Uchiyama, N., Kawamoto, T., Hikichi, Y., Matsumoto, S., Amano, N., Zhang, L., Hosfield, D., Skene, R., Zou, H., Cao, X., Ichikawa, T.

(2013) Bioorg Med Chem Lett 23: 3662-3666

  • DOI: https://doi.org/10.1016/j.bmcl.2013.02.083
  • Primary Citation of Related Structures:  
    4J52, 4J53

  • PubMed Abstract: 

    Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.

    • Organizational Affiliation: 

    Takeda California, 10410 Science Center Drive, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase PLK1293Homo sapiensMutation(s): 1 
Gene Names: PLK1, PLK
EC: 2.7.11.21
UniProt & NIH Common Fund Data Resources
Find proteins for P53350 (Homo sapiens)
Explore P53350 
Go to UniProtKB:  P53350
PHAROS:  P53350
GTEx:  ENSG00000166851 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53350
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1J3
Query on 1J3
Download Ideal Coordinates CCD File 
B [auth A]4-{[(7R)-9-cyclopentyl-7-ethenyl-7-fluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl]amino}-3-methoxy-N-(4-methylpiperazin-1-yl)benzamide
C28 H37 F N8 O3
IVRPFXYSCCXTAK-MUUNZHRXSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT
Download Ideal Coordinates CCD File 
D [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
1J3 BindingDB:  4J52 IC50: 3 (nM) from 1 assay(s)
PDBBind:  4J52 IC50: 3 (nM) from 1 assay(s)
Binding MOAD:  4J52 IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.198 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.873α = 90
b = 66.873β = 90
c = 152.49γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection

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: 2013-05-29
    Type: Initial release
  • Version 1.1: 2013-06-05
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations