3FR4

N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte Fatty-Acid Binding Protein (A-FABP) inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte fatty-acid binding protein (A-FABP) inhibitors.

Barf, T.Lehmann, F.Hammer, K.Haile, S.Axen, E.Medina, C.Uppenberg, J.Svensson, S.Rondahl, L.Lundback, T.

(2009) Bioorg Med Chem Lett 19: 1745-1748

  • DOI: https://doi.org/10.1016/j.bmcl.2009.01.084
  • Primary Citation of Related Structures:  
    3FR2, 3FR4, 3FR5

  • PubMed Abstract: 

    Small molecule inhibitors of adipocyte fatty-acid binding protein (A-FABP) have gained renewed interest following the recent publication of pharmacologically beneficial effects of such inhibitors. Despite the potential utility of selective A-FABP inhibitors within the fields of metabolic disease, inflammation and atherosclerosis, there are few examples of useful A-FABP inhibitors in the public domain. Herein, we describe the optimization of N-benzyl-tetrahydrocarbazole derivatives through the use of co-crystal structure guided medicinal chemistry efforts. This led to the identification of a potent and selective class of A-FABP inhibitors as illustrated by N-benzyl-hexahydrocyclohepta[b]indole 30.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Biovitrum AB, Research, 112 76 Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fatty acid-binding protein, adipocyte132Homo sapiensMutation(s): 0 
Gene Names: FABP4
UniProt & NIH Common Fund Data Resources
Find proteins for P15090 (Homo sapiens)
Explore P15090 
Go to UniProtKB:  P15090
PHAROS:  P15090
GTEx:  ENSG00000170323 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15090
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
F8A
Query on F8A

Download Ideal Coordinates CCD File 
B [auth A]9-[2-(trifluoromethyl)benzyl]-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid
C21 H18 F3 N O2
XAYKLHUEULGGGJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
F8A PDBBind:  3FR4 IC50: 650 (nM) from 1 assay(s)
Binding MOAD:  3FR4 IC50: 49 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.034α = 90
b = 53.628β = 90
c = 31.896γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-03-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations