3KOO

Crystal Structure of soluble epoxide Hydrolase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.307 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.218 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.

Eldrup, A.B.Soleymanzadeh, F.Farrow, N.A.Kukulka, A.De Lombaert, S.

(2010) Bioorg Med Chem Lett 20: 571-575

  • DOI: https://doi.org/10.1016/j.bmcl.2009.11.091
  • Primary Citation of Related Structures:  
    3KOO

  • PubMed Abstract: 

    Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, United States. anne.eldrup@boehringer-ingelheim.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epoxide hydrolase 2555Homo sapiensMutation(s): 0 
Gene Names: EPHX2
EC: 3.3.2.10
UniProt & NIH Common Fund Data Resources
Find proteins for P34913 (Homo sapiens)
Explore P34913 
Go to UniProtKB:  P34913
PHAROS:  P34913
GTEx:  ENSG00000120915 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP34913
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
24D
Query on 24D

Download Ideal Coordinates CCD File 
B [auth A]N-(2,4-dichlorobenzyl)-4-(pyrimidin-2-yloxy)piperidine-1-carboxamide
C17 H18 Cl2 N4 O2
UZEPPAOAIDTLTK-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
24D BindingDB:  3KOO IC50: min: 15, max: 63 (nM) from 3 assay(s)
PDBBind:  3KOO IC50: 15 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.307 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.218 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.765α = 90
b = 91.765β = 90
c = 242.516γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-04-28 
  • Deposition Author(s): Farrow, N.A.

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-02-24
    Changes: Derived calculations
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references