2XP4

DISCOVERY OF CELL-ACTIVE PHENYL-IMIDAZOLE PIN1 INHIBITORS BY STRUCTURE-GUIDED FRAGMENT EVOLUTION


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Discovery of Cell-Active Phenyl-Imidazole Pin1 Inhibitors by Structure-Guided Fragment Evolution.

Potter, A.Oldfield, V.Nunns, C.Fromont, C.Ray, S.Northfield, C.J.Bryant, C.J.Scrace, S.F.Robinson, D.Matossova, N.Baker, L.Dokurno, P.Surgenor, A.E.Davis, B.Richardson, C.M.Murray, J.B.Moore, J.D.

(2010) Bioorg Med Chem Lett 20: 6483

  • DOI: https://doi.org/10.1016/j.bmcl.2010.09.063
  • Primary Citation of Related Structures:  
    2XP3, 2XP4, 2XP5, 2XP6, 2XP7, 2XP8, 2XP9, 2XPA, 2XPB, 3ODK

  • PubMed Abstract: 

    Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.


  • Organizational Affiliation

    Vernalis (R&D) Ltd, Granta Park, Great Abington, Cambridge CB21 6GB, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEPTIDYL-PROLYL CIS-TRANS ISOMERASE NIMA-INTERACTING 1167Homo sapiensMutation(s): 1 
EC: 5.2.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for Q13526 (Homo sapiens)
Explore Q13526 
Go to UniProtKB:  Q13526
PHAROS:  Q13526
GTEx:  ENSG00000127445 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13526
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
12P
Query on 12P

Download Ideal Coordinates CCD File 
B [auth A]DODECAETHYLENE GLYCOL
C24 H50 O13
WRZXKWFJEFFURH-UHFFFAOYSA-N
G14
Query on G14

Download Ideal Coordinates CCD File 
C [auth A]2-phenyl-1H-imidazole-4-carboxylic acid
C10 H8 N2 O2
XCAXKZJNJCKTQH-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
G14 Binding MOAD:  2XP4 IC50: 1.80e+5 (nM) from 1 assay(s)
PDBBind:  2XP4 IC50: 1.80e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.542α = 90
b = 68.542β = 90
c = 79.722γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-12
    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: 2019-01-30
    Changes: Data collection, Experimental preparation, Other
  • Version 1.4: 2019-02-06
    Changes: Data collection, Experimental preparation
  • Version 1.5: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description