2XP3

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

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.219 

Starting Model: experimental
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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
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(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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
B21 BindingDB:  2XP3 IC50: 1.00e+6 (nM) from 1 assay(s)
PDBBind:  2XP3 IC50: 1.00e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.219 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.2α = 90
b = 68.2β = 90
c = 80.068γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling
AMoREphasing

Structure Validation

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Entry History 

Deposition Data

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