4I0E

Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.300 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.233 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors.

Xu, Y.Z.Yuan, S.Bowers, S.Hom, R.K.Chan, W.Sham, H.L.Zhu, Y.L.Beroza, P.Pan, H.Brecht, E.Yao, N.Lougheed, J.Yan, J.Tam, D.Ren, Z.Ruslim, L.Bova, M.P.Artis, D.R.

(2013) Bioorg Med Chem Lett 23: 3075-3080

  • DOI: https://doi.org/10.1016/j.bmcl.2013.03.009
  • Primary Citation of Related Structures:  
    4I0D, 4I0E, 4I0F, 4I12, 4I1C

  • PubMed Abstract: 

    Utilizing a structure based design approach, combined with extensive medicinal chemistry execution, highly selective, potent and novel BACE1 inhibitor 8 (BACE1 Alpha assay IC50=8nM) was made from a weak μM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed.


  • Organizational Affiliation

    Department of Chemical Sciences, Elan Pharmaceuticals, 180 Oyster Point Boulevard, South San Francisco, CA 94080, USA. ying_zi_xu@yahoo.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1406Homo sapiensMutation(s): 0 
Gene Names: BACE1BACEKIAA1149
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.300 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.233 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.062α = 90
b = 103.335β = 90
c = 100.306γ = 90
Software Package:
Software NamePurpose
StructureStudiodata collection
MOLREPphasing
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-06
    Type: Initial release
  • Version 1.1: 2013-07-03
    Changes: Database references