4AKN

N-Terminal Bromodomain of Human BRD2 With tbutyl-phenyl-amino- dimethyl-oxazolyl-quinoline-carboxylic acid

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.170 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Identification of a Novel Series of Bet Family Bromodomain Inhibitors: Binding Mode and Profile of I-Bet151 (Gsk1210151A).

Seal, J., Lamotte, Y., Donche, F., Bouillot, A., Mirguet, O., Gellibert, F., Nicodeme, E., Krysa, G., Kirilovsky, J., Beinke, S., Mccleary, S., Rioja, I., Bamborough, P., Chung, C., Gordon, L., Lewis, T., Walker, A.L., Cutler, L., Lugo, D., Wilson, D.M., Witherington, J., Lee, K., Prinjha, R.K.

(2012) Bioorg Med Chem Lett 22: 2968

  • DOI: https://doi.org/10.1016/j.bmcl.2012.02.041
  • Primary Citation of Related Structures:  
    4AKN, 4ALG

  • PubMed Abstract: 

    A novel series of quinoline isoxazole BET family bromodomain inhibitors are discussed. Crystallography is used to illustrate binding modes and rationalize their SAR. One member, I-BET151 (GSK1210151A), shows good oral bioavailability in both the rat and minipig as well as demonstrating efficient suppression of bacterial induced inflammation and sepsis in a murine in vivo endotoxaemia model.

    • Organizational Affiliation: 

    Epinova DPU, GlaxoSmithKline R&D, Medicines Research Centre, Stevenage, Hertfordshire, UK. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BROMODOMAIN-CONTAINING PROTEIN 2
A, B, C
153Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P25440 (Homo sapiens)
Explore P25440 
Go to UniProtKB:  P25440
PHAROS:  P25440
GTEx:  ENSG00000204256 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP25440
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
S5B
Query on S5B
Download Ideal Coordinates CCD File 
E [auth A],
H [auth B]		4-[(2-tert-butylphenyl)amino]-7-(3,5-dimethyl-1,2-oxazol-4-yl)quinoline-3-carboxylic acid
C25 H25 N3 O3
OWUQUQCSBQATFQ-UHFFFAOYSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
J [auth C]		SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
DMS
Query on DMS
Download Ideal Coordinates CCD File 
I [auth C]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
D [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
S5B PDBBind:  4AKN IC50: 790 (nM) from 1 assay(s)
BindingDB:  4AKN IC50: 794.33 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.170 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114.314α = 90
b = 55.73β = 94.34
c = 67.991γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-04
    Type: Initial release
  • Version 1.1: 2012-11-14
    Changes: Database references
  • Version 1.2: 2019-05-15
    Changes: Advisory, Data collection, Experimental preparation, Other
  • Version 1.3: 2024-05-08
    Changes: Advisory, Data collection, Database references, Derived calculations, Other