3PEQ

PPARd complexed with a phenoxyacetic acid partial agonist


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Phenoxyacetic acid PPARd partial agonists for the treatment of type 2 diabetes: synthesis, optimization, and in vivo efficacy

Evans, K.A.Shearer, B.G.Wisnoski, D.D.Shi, D.Sparks, S.M.Sternbach, D.D.Winegar, D.A.Billin, A.N.Britt, C.Way, J.M.Epperly, A.H.Leesnitzer, L.M.Merrihew, R.V.Xu, R.X.Lambert, M.H.Jin, J.

(2011) Bioorg Med Chem Lett 21: 2345-2350

  • DOI: https://doi.org/10.1016/j.bmcl.2011.02.077
  • Primary Citation of Related Structures:  
    3PEQ

  • PubMed Abstract: 

    A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.


  • Organizational Affiliation

    Discovery Medicinal Chemistry, Discovery Research, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, United States. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peroxisome proliferator-activated receptor delta
A, B
271Homo sapiensMutation(s): 0 
Gene Names: NR1C2PPARBPPARD
UniProt & NIH Common Fund Data Resources
Find proteins for Q03181 (Homo sapiens)
Explore Q03181 
Go to UniProtKB:  Q03181
PHAROS:  Q03181
GTEx:  ENSG00000112033 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ03181
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3EQ
Query on 3EQ

Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]
[(4-{butyl[2-methyl-4'-(methylsulfanyl)biphenyl-3-yl]sulfamoyl}naphthalen-1-yl)oxy]acetic acid
C30 H31 N O5 S2
XUMLNRUSPQDSIN-UHFFFAOYSA-N
JZR
Query on JZR

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
K [auth B]
hexyl beta-D-glucopyranoside
C12 H24 O6
JVAZJLFFSJARQM-RMPHRYRLSA-N
IOD
Query on IOD

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
L [auth B]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
L [auth B],
M [auth B]
IODIDE ION
I
XMBWDFGMSWQBCA-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
3EQ PDBBind:  3PEQ IC50: 31.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.472α = 90
b = 95.535β = 97.76
c = 96.537γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-12
    Type: Initial release
  • Version 1.1: 2014-10-08
    Changes: Database references
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Refinement description, Structure summary