2QMG

Structure of BACE Bound to SCH745966


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.89 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.185 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.

Iserloh, U.Pan, J.Stamford, A.W.Kennedy, M.E.Zhang, Q.Zhang, L.Parker, E.M.McHugh, N.A.Favreau, L.Strickland, C.Voigt, J.

(2008) Bioorg Med Chem Lett 18: 418-422

  • DOI: https://doi.org/10.1016/j.bmcl.2007.10.053
  • Primary Citation of Related Structures:  
    2QMG

  • PubMed Abstract: 

    Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.


  • Organizational Affiliation

    Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ulrich.iserloh@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B
395Homo 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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SC6
Query on SC6

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R,4R)-4-PHENOXYPYRROLIDIN-2-YL]ETHYL}-3-{[(2R)-2-(METHOXYMETHYL)PYRROLIDIN-1-YL]CARBONYL}-5-METHYLBENZAMIDE
C34 H39 F2 N3 O5
KYHYNSQLYDXSNK-MXWGZHRFSA-N
TAR
Query on TAR

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
D(-)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-LWMBPPNESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SC6 Binding MOAD:  2QMG Ki: 0.7 (nM) from 1 assay(s)
PDBBind:  2QMG Ki: 0.7 (nM) from 1 assay(s)
BindingDB:  2QMG IC50: min: 0.7, max: 21 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.89 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.549α = 90
b = 89.288β = 90
c = 130.754γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description