4HBP

Crystal Structure of FAAH in complex with inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.91 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors.

Kono, M.Matsumoto, T.Kawamura, T.Nishimura, A.Kiyota, Y.Oki, H.Miyazaki, J.Igaki, S.Behnke, C.A.Shimojo, M.Kori, M.

(2013) Bioorg Med Chem 21: 28-41

  • DOI: https://doi.org/10.1016/j.bmc.2012.11.006
  • Primary Citation of Related Structures:  
    4HBP

  • PubMed Abstract: 

    A series of piperazine ureas was designed, synthesized, and evaluated for their potential as novel orally available fatty acid amide hydrolase (FAAH) inhibitors that are therapeutically effective against pain. We carried out an optimization study of the lead compound 3 to improve its DMPK profile as well as in vitro potency. We identified the thiazole compound 60j with potent inhibitory activity, high brain permeability, and good bioavailability. Compound 60j showed a potent and dose-dependent anti-nociceptive effect in the acetic acid-induced writhing test in mice.


  • Organizational Affiliation

    Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. mitsunori.kouno@takeda.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fatty-acid amide hydrolase 1
A, B
550Rattus norvegicusMutation(s): 0 
Gene Names: FaahFaah1
EC: 3.5.1.99
UniProt
Find proteins for P97612 (Rattus norvegicus)
Explore P97612 
Go to UniProtKB:  P97612
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP97612
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
17J
Query on 17J

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
4-(3-phenyl-1,2,4-thiadiazol-5-yl)-N-(pyridin-3-yl)piperazine-1-carboxamide
C18 H18 N6 O S
RCAFZHFLIBYWGO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
17J PDBBind:  4HBP IC50: 3.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.91 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.92α = 90
b = 103.92β = 90
c = 251.965γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-02-06
    Type: Initial release
  • Version 1.1: 2023-09-20
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description