5XMX

Co-crystal structure of Inhibitor compound in complex with human PPARdelta LBD

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

Novel highly selective peroxisome proliferator-activated receptor delta (PPAR delta) modulators with pharmacokinetic properties suitable for once-daily oral dosing.

Lagu, B., Kluge, A.F., Fredenburg, R.A., Tozzo, E., Senaiar, R.S., Jaleel, M., Panigrahi, S.K., Tiwari, N.K., Krishnamurthy, N.R., Takahashi, T., Patane, M.A.

(2017) Bioorg Med Chem Lett 27: 5230-5234

  • DOI: https://doi.org/10.1016/j.bmcl.2017.10.037
  • Primary Citation of Related Structures:  
    5XMX

  • PubMed Abstract: 

    Optimization of benzamide PPARδ modulator 1 led to (E)-6-(2-((4-(furan-2-yl)-N-methylbenzamido)methyl)phenoxy)-4-methylhex-4-enoic acid (18), a potent selective PPARδ modulator with significantly improved exposure in multiple species following oral administration.

    • Organizational Affiliation: 

    Mitobridge, Inc., 1030 Massachusetts Ave., Cambridge, MA 02138, United States. Electronic address: blagu@mitobridge.com.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peroxisome proliferator-activated receptor delta
A, B
275Homo sapiensMutation(s): 0 
Gene Names: PPARD, NR1C2, PPARB
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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
89L
Query on 89L
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		(E)-6-[2-[[[4-(furan-2-yl)phenyl]carbonyl-methyl-amino]methyl]phenoxy]-4-methyl-hex-4-enoic acid
C26 H27 N O5
WZFMWAHUFRLQRH-XDJHFCHBSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
89L BindingDB:  5XMX Kd: 57 (nM) from 1 assay(s)
EC50: min: 5, max: 270 (nM) from 7 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.84α = 90
b = 76.39β = 97.74
c = 96.73γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata processing
XDSdata reduction
XDSdata scaling
SCALEPACKdata scaling

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: 2018-05-23
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Refinement description