3IKG

Structure-Based Design of Novel PIN1 Inhibitors (I)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structure-based design of novel human Pin1 inhibitors (I).

Guo, C.Hou, X.Dong, L.Dagostino, E.Greasley, S.Ferre, R.Marakovits, J.Johnson, M.C.Matthews, D.Mroczkowski, B.Parge, H.Vanarsdale, T.Popoff, I.Piraino, J.Margosiak, S.Thomson, J.Los, G.Murray, B.W.

(2009) Bioorg Med Chem Lett 19: 5613-5616

  • DOI: https://doi.org/10.1016/j.bmcl.2009.08.034
  • Primary Citation of Related Structures:  
    3IK8, 3IKD, 3IKG

  • PubMed Abstract: 

    Pin1 is a member of the cis-trans peptidyl-prolyl isomerase family with potential anti-cancer therapeutic value. Here we report structure-based de novo design and optimization of novel Pin1 inhibitors. Without a viable lead from internal screenings, we designed a series of novel Pin1 inhibitors by interrogating and exploring a protein crystal structure of Pin1. The ligand efficiency of the initial concept molecule was optimized with integrated SBDD and parallel chemistry approaches, resulting in a more attractive lead series.


  • Organizational Affiliation

    Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, CA 92121, USA. alex.guo@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
A, B
123Homo sapiensMutation(s): 2 
Gene Names: PIN1
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
J8Z
Query on J8Z

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(2R)-2-[(1-benzothiophen-2-ylcarbonyl)amino]-3-(3-methylphenyl)propyl phosphate
C19 H18 N O5 P S
VJUQXEZAYUVHJF-MRXNPFEDSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
J8Z PDBBind:  3IKG Ki: 57 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.255α = 90
b = 36.53β = 100.4
c = 51.32γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SHELXmodel building
SHELXL-97refinement
DENZOdata reduction
SCALEPACKdata scaling
SHELXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2016-03-30
    Changes: Other
  • Version 1.3: 2018-01-24
    Changes: Structure summary
  • Version 1.4: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-09-06
    Changes: Data collection, Refinement description