4AFJ

5-aryl-4-carboxamide-1,3-oxazoles: potent and selective GSK-3 inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

5-Aryl-4-Carboxamide-1,3-Oxazoles: Potent and Selective Gsk-3 Inhibitors.

Gentile, G.Merlo, G.Pozzan, A.Bernasconi, G.Bax, B.Bamborough, P.Bridges, A.Carter, P.Neu, M.Yao, G.Brough, C.Cutler, G.Coffin, A.Belyanskaya, S.

(2012) Bioorg Med Chem Lett 22: 1989

  • DOI: https://doi.org/10.1016/j.bmcl.2012.01.034
  • Primary Citation of Related Structures:  
    4AFJ

  • PubMed Abstract: 

    5-Aryl-4-carboxamide-1,3-oxazoles are a novel, potent and selective series of GSK-3 inhibitors. The optimization of the series to yield compounds with cell activity and brain permeability is described.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Neuroscience Centre of Excellence of Drug Discovery, GlaxoSmithKline, Via A Fleming 4, 37135 Verona, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLYCOGEN SYNTHASE KINASE-3 BETA
A, B
367Homo sapiensMutation(s): 0 
EC: 2.7.11.26 (PDB Primary Data), 2.7.11.1 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P49841 (Homo sapiens)
Explore P49841 
Go to UniProtKB:  P49841
PHAROS:  P49841
GTEx:  ENSG00000082701 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49841
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PROTO-ONCOGENE FRAT1C [auth X],
D [auth Y]
30Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q92837 (Homo sapiens)
Explore Q92837 
Go to UniProtKB:  Q92837
PHAROS:  Q92837
GTEx:  ENSG00000165879 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ92837
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SJJ
Query on SJJ

Download Ideal Coordinates CCD File 
K [auth A],
S [auth B]
5-(4-METHOXYPHENYL)-N-(PYRIDIN-4-YLMETHYL)-1,3-OXAZOLE-4-CARBOXAMIDE
C17 H15 N3 O3
NDXJIXWTFPGHAI-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
L [auth B]
M [auth B]
E [auth A],
F [auth A],
G [auth A],
L [auth B],
M [auth B],
N [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
J [auth A]
O [auth B]
P [auth B]
H [auth A],
I [auth A],
J [auth A],
O [auth B],
P [auth B],
Q [auth B],
R [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A, B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
SJJ BindingDB:  4AFJ IC50: min: 79, max: 1995 (nM) from 3 assay(s)
PDBBind:  4AFJ IC50: 398 (nM) from 1 assay(s)
Binding MOAD:  4AFJ IC50: 398 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 152.317α = 90
b = 152.317β = 90
c = 199.054γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-02-29
    Type: Initial release
  • Version 1.1: 2012-03-07
    Changes: Other
  • Version 1.2: 2019-05-08
    Changes: Data collection, Derived calculations, Experimental preparation, Other
  • Version 1.3: 2019-05-29
    Changes: Data collection, Experimental preparation
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description