2QU2

BACE1 with Compound 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Thiophene substituted acylguanidines as BACE1 inhibitors.

Fobare, W.F.Solvibile, W.R.Robichaud, A.J.Malamas, M.S.Manas, E.Turner, J.Hu, Y.Wagner, E.Chopra, R.Cowling, R.Jin, G.Bard, J.

(2007) Bioorg Med Chem Lett 17: 5353-5356

  • DOI: https://doi.org/10.1016/j.bmcl.2007.08.010
  • Primary Citation of Related Structures:  
    2QU2, 2QU3

  • PubMed Abstract: 

    A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.


  • Organizational Affiliation

    Chemical and Screening Sciences, Wyeth Research, CN8000, Princeton, NJ 08543-8000, USA. fobarew@wyeth.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1415Homo sapiensMutation(s): 0 
Gene Names: BACE1BACE
EC: 3.4.23.46
UniProt & NIH Common Fund Data Resources
Find proteins for P56817 (Homo sapiens)
Explore P56817 
Go to UniProtKB:  P56817
PHAROS:  P56817
GTEx:  ENSG00000186318 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56817
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
251
Query on 251

Download Ideal Coordinates CCD File 
B [auth A]N-[amino(imino)methyl]-2-(2,5-diphenyl-1H-pyrrol-1-yl)acetamide
C19 H18 N4 O
WVLDNAVUCUAGDP-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
251 BindingDB:  2QU2 IC50: 3700 (nM) from 1 assay(s)
PDBBind:  2QU2 IC50: 3700 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.218 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.916α = 90
b = 104.845β = 95
c = 50.483γ = 90
Software Package:
Software NamePurpose
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2008-08-05 
  • Deposition Author(s): Chopra, R.

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-05
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance