1SQT

Substituted 2-Naphthamidine Inhibitors of Urokinase

PDB DOI: https://doi.org/10.2210/pdb1SQT/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2004-03-19 Released: 2004-04-27
Deposition Author(s): Wendt, M.D., Geyer, A., McClellan, W.J., Rockway, T.W., Weitzberg, M., Zhang, X., Mantei, R., Stewart, K., Nienaber, V., Klinghofer, V., Giranda, V.L.

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

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 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

PubMed: 15149645 Search on PubMed
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. [email protected]

Macromolecule Content

Total Structure Weight: 27.97 kDa
Atom Count: 2,032
Modelled Residue Count: 245
Deposited Residue Count: 245
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Urokinase-type plasminogen activator	A	245	Homo sapiens	Mutation(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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00749
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
UI3 Query on UI3 Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	7-METHOXY-8-[1-(METHYLSULFONYL)-1H-PYRAZOL-4-YL]NAPHTHALENE-2-CARBOXIMIDAMIDE C₁₆ H₁₆ N₄ O₃ S KQUXAFOLFXHVQN-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
UI3	BindingDB: 1SQT	Ki: min: 630, max: 631 (nM) from 3 assay(s)
UI3	PDBBind: 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 = 55.16	α = 90
b = 53	β = 90
c = 82.3	γ = 90

Software Package:

Software Name	Purpose
X-PLOR	refinement

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2004-04-27

Deposition Author(s):

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
Version 1.3: 2024-10-30
Changes: Data collection, Database references, Derived calculations, Structure summary