3D15

Crystal structure of mouse Aurora A (Asn186->Gly, Lys240->Arg, Met302->Leu) in complex with 1-(3-chloro-phenyl)-3-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)- ethyl]-thiazol-2-yl}-urea [SNS-314]


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.238 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Discovery of a potent and selective aurora kinase inhibitor.

Oslob, J.D.Romanowski, M.J.Allen, D.A.Baskaran, S.Bui, M.Elling, R.A.Flanagan, W.M.Fung, A.D.Hanan, E.J.Harris, S.Heumann, S.A.Hoch, U.Jacobs, J.W.Lam, J.Lawrence, C.E.McDowell, R.S.Nannini, M.A.Shen, W.Silverman, J.A.Sopko, M.M.Tangonan, B.T.Teague, J.Yoburn, J.C.Yu, C.H.Zhong, M.Zimmerman, K.M.O'Brien, T.Lew, W.

(2008) Bioorg Med Chem Lett 18: 4880-4884

  • DOI: https://doi.org/10.1016/j.bmcl.2008.07.073
  • Primary Citation of Related Structures:  
    3D14, 3D15

  • PubMed Abstract: 

    This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.


  • Organizational Affiliation

    Medicinal Chemistry, Sunesis Pharmaceuticals, 395 Oyster Point Boulevard, South San Francisco, CA 94080, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
serine/threonine kinase 6272Mus musculusMutation(s): 3 
Gene Names: AurkaStk6
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P97477 (Mus musculus)
Explore P97477 
Go to UniProtKB:  P97477
IMPC:  MGI:894678
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP97477
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
AK2
Query on AK2

Download Ideal Coordinates CCD File 
B [auth A]1-(3-chlorophenyl)-3-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-1,3-thiazol-2-yl}urea
C18 H15 Cl N6 O S2
FAYAUAZLLLJJGH-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AK2 BindingDB:  3D15 IC50: min: 9, max: 9 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.238 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.353α = 90
b = 82.353β = 90
c = 171.999γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
CrystalCleardata reduction
d*TREKdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-05-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2013-06-19
    Changes: Database references
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Refinement description