1SQT

Substituted 2-Naphthamidine Inhibitors of Urokinase

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.236 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Interaction with the S1beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.

Wendt, M.D., Geyer, A., McClellan, W.J., Rockway, T.W., Weitzberg, M., Zhao, X., Mantei, R., Stewart, K., Nienaber, V., Klinghofer, V., Giranda, V.L.

(2004) Bioorg Med Chem Lett 14: 3063-3068

  • DOI: https://doi.org/10.1016/j.bmcl.2004.04.030
  • Primary Citation of Related Structures:  
    1SQA, 1SQO, 1SQT

  • PubMed Abstract: 

    Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease urokinase plasminogen activator (uPA) are described. Direct attachment of five-membered saturated or unsaturated rings improved inhibitor performance; substitution with sulfones further improved binding profiles. Combination of these substituents or of previously described NH-linked heteroaromatic rings with 6-phenyl amide substituents provided further enhancements to potency and selectivity.

    • Organizational Affiliation: 

    Cancer Research, Global Pharmaceutical R & D, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6101, USA. mike.d.wendt@abbott.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Urokinase-type plasminogen activator245Homo sapiensMutation(s): 0 
Gene Names: PLAU
EC: 3.4.21.73
UniProt & NIH Common Fund Data Resources
Find proteins for P00749 (Homo sapiens)
Explore P00749 
Go to UniProtKB:  P00749
PHAROS:  P00749
GTEx:  ENSG00000122861 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00749
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UI3
Query on UI3
Download Ideal Coordinates CCD File 
B [auth A]7-METHOXY-8-[1-(METHYLSULFONYL)-1H-PYRAZOL-4-YL]NAPHTHALENE-2-CARBOXIMIDAMIDE
C16 H16 N4 O3 S
KQUXAFOLFXHVQN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
UI3 BindingDB:  1SQT Ki: min: 630, max: 631 (nM) from 3 assay(s)
PDBBind:  1SQT Ki: 630 (nM) from 1 assay(s)
Binding MOAD:  1SQT Ki: 630 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.236 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.16α = 90
b = 53β = 90
c = 82.3γ = 90
Software Package:
Software NamePurpose
X-PLORrefinement

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-04-27
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance