3S2O

Fragment based discovery and optimisation of bace-1 inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Fragment-based discovery and optimization of BACE1 inhibitors.

Madden, J.Dod, J.R.Godemann, R.Kraemer, J.Smith, M.Biniszkiewicz, M.Hallett, D.J.Barker, J.Dyekjaer, J.D.Hesterkamp, T.

(2010) Bioorg Med Chem Lett 20: 5329-5333

  • DOI: https://doi.org/10.1016/j.bmcl.2010.06.089
  • Primary Citation of Related Structures:  
    3MSJ, 3MSK, 3MSL, 3S2O

  • PubMed Abstract: 

    A novel series of 2-aminobenzimidazole inhibitors of BACE1 has been discovered using fragment-based drug discovery (FBDD) techniques. The rapid optimization of these inhibitors using structure-guided medicinal chemistry is discussed.


  • Organizational Affiliation

    Evotec UK Ltd, Abingdon, UK. james.madden@evotec.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1408Homo sapiensMutation(s): 0 
Gene Names: BACEBACE1KIAA1149
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
EV6
Query on EV6

Download Ideal Coordinates CCD File 
B [auth A](3S)-3-(2-amino-5-chloro-1H-benzimidazol-1-yl)-N-[(1R,3S,5R,7R)-tricyclo[3.3.1.1~3,7~]dec-2-yl]pentanamide
C22 H29 Cl N4 O
KMAKOMVKNWTGPE-LIXZBVSLSA-N
IOD
Query on IOD

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
IODIDE ION
I
XMBWDFGMSWQBCA-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
EV6 BindingDB:  3S2O IC50: 8900 (nM) from 1 assay(s)
PDBBind:  3S2O IC50: 8900 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.208 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.88α = 90
b = 101.88β = 90
c = 170.181γ = 120
Software Package:
Software NamePurpose
DNAdata collection
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata 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: 2011-06-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-09-07
    Changes: Structure summary
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description