2XRU

AURORA-A T288E COMPLEXED WITH PHA-828300


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.344 
  • R-Value Work: 0.247 
  • R-Value Observed: 0.247 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Thieno[3,2-C]Pyrazoles: A Novel Class of Aurora Inhibitors with Favorable Antitumor Activity.

Bindi, S.Fancelli, D.Alli, C.Berta, D.Bertrand, J.A.Cameron, A.D.Cappella, P.Carpinelli, P.Cervi, G.Croci, V.D'Anello, M.Forte, B.Laura Giorgini, M.Marsiglio, A.Moll, J.Pesenti, E.Pittala, V.Pulici, M.Riccardi-Sirtori, F.Roletto, F.Soncini, C.Storici, P.Varasi, M.Volpi, D.Zugnoni, P.Vianello, P.

(2010) Bioorg Med Chem 18: 7113

  • DOI: https://doi.org/10.1016/j.bmc.2010.07.048
  • Primary Citation of Related Structures:  
    2XRU

  • PubMed Abstract: 

    A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.


  • Organizational Affiliation

    Nerviano Medical Sciences-Oncology, via Pasteur 10, 20014 Nerviano, Milan, Italy. simona.bindi@nervianoms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SERINE/THREONINE-PROTEIN KINASE 6280Homo sapiensMutation(s): 1 
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
400
Query on 400

Download Ideal Coordinates CCD File 
B [auth A]3-({[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]CARBONYL}AMINO)-N-[(1R)-1-PHENYLPROPYL]-1H-THIENO[3,2-C]PYRAZOLE-5-CARBOXAMIDE
C27 H30 N6 O2 S
BGKRQXRINOKEMF-OAQYLSRUSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
400 PDBBind:  2XRU IC50: 31 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.344 
  • R-Value Work: 0.247 
  • R-Value Observed: 0.247 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.467α = 90
b = 82.467β = 90
c = 165.453γ = 120
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-29
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-04-03
    Changes: Data collection, Other, Source and taxonomy
  • Version 1.4: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other