4LR6

Structure of BRD4 bromodomain 1 with a 3-methyl-4-phenylisoxazol-5-amine fragment


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.29 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.216 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors.

Gehling, V.S.Hewitt, M.C.Vaswani, R.G.Leblanc, Y.Cote, A.Nasveschuk, C.G.Taylor, A.M.Harmange, J.C.Audia, J.E.Pardo, E.Joshi, S.Sandy, P.Mertz, J.A.Sims, R.J.Bergeron, L.Bryant, B.M.Bellon, S.Poy, F.Jayaram, H.Sankaranarayanan, R.Yellapantula, S.Bangalore Srinivasamurthy, N.Birudukota, S.Albrecht, B.K.

(2013) ACS Med Chem Lett 4: 835-840

  • DOI: https://doi.org/10.1021/ml4001485
  • Primary Citation of Related Structures:  
    4LR6, 4LRG

  • PubMed Abstract: 

    The identification of a novel series of small molecule BET inhibitors is described. Using crystallographic binding modes of an amino-isoxazole fragment and known BET inhibitors, a structure-based drug design effort lead to a novel isoxazole azepine scaffold. This scaffold showed good potency in biochemical and cellular assays and oral activity in an in vivo model of BET inhibition.


  • Organizational Affiliation

    Constellation Pharmaceuticals , 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bromodomain-containing protein 4128Homo sapiensMutation(s): 0 
Gene Names: BRD4BRD4_HUMANHUNK1
UniProt & NIH Common Fund Data Resources
Find proteins for O60885 (Homo sapiens)
Explore O60885 
Go to UniProtKB:  O60885
PHAROS:  O60885
GTEx:  ENSG00000141867 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60885
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
1XA BindingDB:  4LR6 IC50: min: 2.00e+4, max: 3.30e+4 (nM) from 2 assay(s)
Binding MOAD:  4LR6 IC50: 3.30e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.29 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 32.682α = 90
b = 47.131β = 90
c = 77.794γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2013-08-07
    Type: Initial release
  • Version 1.1: 2013-08-14
    Changes: Structure summary
  • Version 1.2: 2014-10-08
    Changes: Database references
  • Version 1.3: 2017-11-15
    Changes: Refinement description
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description