3N4L

BACE-1 in complex with ELN380842


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Improving the permeability of the hydroxyethylamine BACE-1 inhibitors: structure-activity relationship of P2' substituents.

Truong, A.P.Probst, G.D.Aquino, J.Fang, L.Brogley, L.Sealy, J.M.Hom, R.K.Tucker, J.A.John, V.Tung, J.S.Pleiss, M.A.Konradi, A.W.Sham, H.L.Dappen, M.S.Toth, G.Yao, N.Brecht, E.Pan, H.Artis, D.R.Ruslim, L.Bova, M.P.Sinha, S.Yednock, T.A.Zmolek, W.Quinn, K.P.Sauer, J.M.

(2010) Bioorg Med Chem Lett 20: 4789-4794

  • DOI: https://doi.org/10.1016/j.bmcl.2010.06.112
  • Primary Citation of Related Structures:  
    3N4L

  • PubMed Abstract: 

    Herein we describe further evolution of hydroxyethylamine inhibitors of BACE-1 with enhanced permeability characteristics necessary for CNS penetration. Variation at the P2' position of the inhibitor with more polar substituents led to compounds 19 and 32, which retained the potency of more lipophilic analog 1 but with much higher observed passive permeability in MDCK cellular assay.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Elan Pharmaceuticals, 180 Oyster Point Boulevard, South San Francisco, CA 94080, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B, C
406Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
842
Query on 842

Download Ideal Coordinates CCD File 
D [auth A],
E [auth B],
F [auth C]
N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(1H-pyrazol-1-yl)phenyl]cyclohexyl}amino)propyl]acetamide
C27 H32 F2 N4 O2
QXNFPOMRKODYSK-IZZNHLLZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
842 BindingDB:  3N4L IC50: 59 (nM) from 1 assay(s)
PDBBind:  3N4L IC50: 59 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.047α = 90
b = 105.582β = 104.63
c = 101.575γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
MOLREPphasing
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-11-24 
  • Deposition Author(s): Yao, N.H.

Revision History  (Full details and data files)

  • Version 1.0: 2010-11-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description