1QXK

Monoacid-Based, Cell Permeable, Selective Inhibitors of Protein Tyrosine Phosphatase 1B


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Identification of a Monoacid-Based, Cell Permeable, Selective Inhibitor of Protein Tyrosine Phosphatase 1B

Xin, Z.Liu, G.Abad-Zapatero, C.Pei, Z.Szczepankiewick, B.G.Li, X.Zhang, T.Hutchins, C.W.Hajduk, P.J.Ballaron, S.J.Stashko, M.A.Lubben, T.H.Trevillyan, J.M.Jirousek, M.R.

(2003) Bioorg Med Chem Lett 13: 3947-3950

  • DOI: https://doi.org/10.1016/j.bmcl.2003.08.064
  • Primary Citation of Related Structures:  
    1QXK

  • PubMed Abstract: 

    Monoacid-based PTP1B inhibitors with improved physiochemical properties have been investigated. A (2-hydroxy-phenoxy) acetic acid-based phosphotyrosyl mimetic has been linked with an optimized second arylphosphate binding site ligand to produce compound 20 with low micromolar potency against PTP1B, good selectivity over TCPTP (20-fold) and high cell permeability in the Caco-2 system.


  • Organizational Affiliation

    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. zhili.xin@abbott.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein-tyrosine phosphatase, non-receptor type 1321Homo sapiensMutation(s): 0 
Gene Names: PTPN1 OR PTP1B
EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for P18031 (Homo sapiens)
Explore P18031 
Go to UniProtKB:  P18031
PHAROS:  P18031
GTEx:  ENSG00000196396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP18031
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
429
Query on 429

Download Ideal Coordinates CCD File 
B [auth A]2-{4-[2-ACETYLAMINO-3-(4-CARBOXYMETHOXY-3-HYDROXY-PHENYL)-PROPIONYLAMINO]-BUTOXY}-6-HYDROXY-BENZOIC ACID METHYL ESTER
C25 H30 N2 O10
QEANZBIJPCAREV-KRWDZBQOSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
429 BindingDB:  1QXK Ki: min: 7943, max: 9000 (nM) from 2 assay(s)
IC50: 9000 (nM) from 1 assay(s)
PDBBind:  1QXK Ki: 9000 (nM) from 1 assay(s)
Binding MOAD:  1QXK Ki: 9000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.201 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.356α = 90
b = 88.356β = 90
c = 104.347γ = 120
Software Package:
Software NamePurpose
CNXrefinement
MAR345data collection
HKL-2000data scaling
CNXphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-10-28
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description