3MYG

Aurora A Kinase complexed with SCH 1473759


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of a Potent, Injectable Inhibitor of Aurora Kinases Based on the Imidazo-[1,2-a]-Pyrazine Core.

Yu, T.Tagat, J.R.Kerekes, A.D.Doll, R.J.Zhang, Y.Xiao, Y.Esposite, S.Belanger, D.B.Curran, P.J.Mandal, A.K.Siddiqui, M.A.Shih, N.Y.Basso, A.D.Liu, M.Gray, K.Tevar, S.Jones, J.Lee, S.Liang, L.Ponery, S.Smith, E.B.Hruza, A.Voigt, J.Ramanathan, L.Prosise, W.Hu, M.

(2010) ACS Med Chem Lett 1: 214-218

  • DOI: https://doi.org/10.1021/ml100063w
  • Primary Citation of Related Structures:  
    3MYG

  • PubMed Abstract: 

    The imidazo-[1,2-a]-pyrazine (1) is a dual inhibitor of Aurora kinases A and B with modest cell potency (IC50 = 250 nM) and low solubility (5 μM). Lead optimization guided by the binding mode led to the acyclic amino alcohol 12k (SCH 1473759), which is a picomolar inhibitor of Aurora kinases (TdF K d Aur A = 0.02 nM and Aur B = 0.03 nM) with improved cell potency (phos-HH3 inhibition IC50 = 25 nM) and intrinsic aqueous solubility (11.4 mM). It also demonstrated efficacy and target engagement in human tumor xenograft mouse models.


  • Organizational Affiliation

    Departments of Chemical Research.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase 6272Homo sapiensMutation(s): 0 
Gene Names: AURKAAIKARK1AURABTAKSTK15STK6
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EML
Query on EML

Download Ideal Coordinates CCD File 
C [auth A]2-{ethyl[(5-{[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]amino}isothiazol-3-yl)methyl]amino}-2-methylpropan-1-ol
C20 H26 N8 O S
RHGZQGXELRMGES-UHFFFAOYSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
B [auth A]TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EML PDBBind:  3MYG Kd: 0.02 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.88α = 90
b = 80.88β = 90
c = 171.282γ = 120
Software Package:
Software NamePurpose
StructureStudiodata collection
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description