3P9J

Aurora A kinase domain with phthalazinone pyrazole inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.204 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history. 


Literature

Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of aurora-a kinase.

Prime, M.E., Courtney, S.M., Brookfield, F.A., Marston, R.W., Walker, V., Warne, J., Boyd, A.E., Kairies, N.A., von der Saal, W., Limberg, A., Georges, G., Engh, R.A., Goller, B., Rueger, P., Rueth, M.

(2011) J Med Chem 54: 312-319

  • DOI: https://doi.org/10.1021/jm101346r
  • Primary Citation of Related Structures:  
    3P9J

  • PubMed Abstract: 

    The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.

    • Organizational Affiliation: 

    Evotec (UK) Ltd., 114 Milton Park, Abingdon, UK. Michael.Prime@evotec.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase 6268Homo sapiensMutation(s): 2 
Gene Names: AIK, ARK1, AURA, AURKA, BTAK, STK15, STK6
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O14965 (Homo sapiens)
Explore O14965 
Go to UniProtKB:  O14965
PHAROS:  O14965
GTEx:  ENSG00000087586 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14965
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P9J
Query on P9J
Download Ideal Coordinates CCD File 
B [auth A]4-[(5-methyl-1H-pyrazol-3-yl)amino]-2-phenylphthalazin-1(2H)-one
C18 H15 N5 O
DSDIWWSXOOXFSI-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
P9J PDBBind:  3P9J IC50: 31 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.204 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.113α = 90
b = 83.113β = 90
c = 169.191γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-03-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-10-05
    Changes: Database references
  • Version 1.3: 2019-07-17
    Changes: Data collection, Refinement description
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations