5G4S

BROMODOMAIN OF HUMAN BRPF1 WITH N-1,3-dimethyl-6-2R-2- methylpiperazin-1-yl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl-N- ethyl-2-methoxybenzamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.187 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Gsk6853, a Chemical Probe for Inhibition of the Brpf1 Bromodomain.

Bamborough, P., Barnett, H.A., Becher, I., Bird, M.J., Chung, C., Craggs, P.D., Demont, E.H., Diallo, H., Fallon, D.J., Gordon, L.J., Grandi, P., Hobbs, C.I., Hooper-Greenhill, E., Jones, E.J., Law, R.P., Le Gall, A., Lugo, D., Michon, A., Mitchell, D.J., Prinjha, R.K., Sheppard, R.J., Watson, A.J.B., Watson, R.J.

(2016) ACS Med Chem Lett 7: 552

  • DOI: https://doi.org/10.1021/acsmedchemlett.6b00092
  • Primary Citation of Related Structures:  
    5G4R, 5G4S

  • PubMed Abstract: 

    The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micromolar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.

    • Organizational Affiliation: 

    Epinova Discovery Performance Unit, Quantitative Pharmacology, Experimental Medicine Unit, Flexible Discovery Unit, and Platform Technology and Science, GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEREGRIN118Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P55201 (Homo sapiens)
Explore P55201 
Go to UniProtKB:  P55201
PHAROS:  P55201
GTEx:  ENSG00000156983 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55201
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8VI
Query on 8VI
Download Ideal Coordinates CCD File 
B [auth A]N-[1,3-dimethyl-6-[(2R)-2-methylpiperazin-1-yl]-2-oxidanylidene-benzimidazol-5-yl]-N-ethyl-2-methoxy-benzamide
C24 H31 N5 O3
WFXIHQFRQPGCCR-MRXNPFEDSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
C [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
8VI BindingDB:  5G4S IC50: min: 1000, max: 3981 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.187 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.53α = 90
b = 60.53β = 90
c = 85.14γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

  • Released Date: 2016-07-06 
    • Deposition Author(s): Chung, C.

Revision History  (Full details and data files)

  • Version 1.0: 2016-07-06
    Type: Initial release
  • Version 1.1: 2018-05-16
    Changes: Data collection
  • Version 1.2: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other