bromodomain containing 2 | Bromodomain kinase (BRDK) family | IUPHAR/BPS Guide to PHARMACOLOGY

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bromodomain containing 2

Target not currently curated in GtoImmuPdb

Target id: 1944

Nomenclature: bromodomain containing 2

Abbreviated Name: BRD2

Family: Bromodomain kinase (BRDK) family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 801 6p21.3 BRD2 bromodomain containing 2
Mouse - 798 17 B1 Brd2 bromodomain containing 2
Rat - 798 20p12 Brd2 bromodomain containing 2
Previous and Unofficial Names
FSRG1 | NAT | Protein RING3
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  N-Terminal Bromodomain of Human BRD2 With IBET-151
PDB Id:  4ALG
Ligand:  I-BET151
Resolution:  1.6Å
Species:  Human
References:  10
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure showing BRD2-BD1 in assocation with the inhibitor BIC1.
PDB Id:  3AQA
Ligand:  BIC1
Resolution:  2.3Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of BRD2(BD2) mutant with ligand ET bromodomain inhibitor.
PDB Id:  4QEW
Ligand:  ET bromodomain inhibitor
Resolution:  1.7Å
Species:  Human
References:  1
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
XD14 Hs Inhibition 6.8 pKd 7
pKd 6.8 (Kd 1.7x10-7 M) [7]
Description: Assay using recombinant BRD2-BD1.
ME bromodomain inhibitor Hs Inhibition 5.8 – 6.5 pKd 1
pKd 5.8 – 6.5 (Kd 1.5x10-6 – 3x10-7 M) The higher affinity interaction is with the BRD2-BD2 domain, the lower affinity with the BRD2-BD1 domain [1]
LY 294002 Hs Inhibition 5.8 pKd 4
pKd 5.8 (Kd 1.41x10-6 M) [4]
ET bromodomain inhibitor Hs Inhibition 4.8 – 5.1 pKd 1
pKd 4.8 – 5.1 (Kd 1.7x10-5 – 9x10-6 M) The higher affinity interaction is with the BRD2-BD1 domain, the lower affinity with the BRD2-BD2 domain [1]
BIC1 Hs Inhibition 4.6 pKd 6
pKd 4.6 (Kd 2.8x10-5 M) [6]
Description: Binding to recombinant BRD2-BD1 protein.
GW841819X Hs Inhibition 7.5 pIC50 2
pIC50 7.5 (IC50 2.99x10-8 M) [2]
Description: Displacement of a tetra-acetylated histone H4 peptide from the tandem BET bromodomains of BRD2.
molibresib Hs Inhibition 7.5 pIC50 2
pIC50 7.5 (IC50 3.25x10-8 M) [2]
Description: Displacement of a tetra-acetylated histone H4 peptide from the tandem BET bromodomains of BRD2.
I-BET151 Hs Inhibition 6.3 pIC50 3
pIC50 6.3 (IC50 5x10-7 M) [3]
compound 38 [PMID: 24000170] Hs Inhibition 6.3 pIC50 9
pIC50 6.3 (IC50 5.01x10-7 M) [9]
compound 36 [PMID: 24000170] Hs Inhibition 6.0 pIC50 9
pIC50 6.0 (IC50 1x10-6 M) [9]
compound 4d [PMID: 21851057] Hs Inhibition 5.8 pIC50 5
pIC50 5.8 (IC50 1.6x10-6 M) [5]
Description: Inhibition of binding to recombinant BRD2-BD1.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RVX 208 Hs Antagonist 7.1 pIC50 8
pIC50 7.1 (IC50 9x10-8 M) [8]
Description: Measured using a TR-FRET assay to evaluate binding to BD2 of BRD2.

References

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1. Baud MGJ, Lin-Shiao E, Cardote T, Tallant C, Pschibul A, Chan KH, Zengerle M, Garcia JR, Kwan TT, Ferguson FM et al.. (2014) Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes. Science, 346 (6209): 638-641. [PMID:25323695]

2. Chung CW, Coste H, White JH, Mirguet O, Wilde J, Gosmini RL, Delves C, Magny SM, Woodward R, Hughes SA et al.. (2011) Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J. Med. Chem., 54 (11): 3827-38. [PMID:21568322]

3. Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, Robson SC, Chung CW, Hopf C, Savitski MM et al.. (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature, 478 (7370): 529-33. [PMID:21964340]

4. Dittmann A, Werner T, Chung CW, Savitski MM, Fälth Savitski M, Grandi P, Hopf C, Lindon M, Neubauer G, Prinjha RK et al.. (2014) The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains. ACS Chem. Biol., 9 (2): 495-502. [PMID:24533473]

5. Hewings DS, Wang M, Philpott M, Fedorov O, Uttarkar S, Filippakopoulos P, Picaud S, Vuppusetty C, Marsden B, Knapp S et al.. (2011) 3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. J. Med. Chem., 54 (19): 6761-70. [PMID:21851057]

6. Ito T, Umehara T, Sasaki K, Nakamura Y, Nishino N, Terada T, Shirouzu M, Padmanabhan B, Yokoyama S, Ito A et al.. (2011) Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors. Chem. Biol., 18 (4): 495-507. [PMID:21513886]

7. Lucas X, Wohlwend D, Hügle M, Schmidtkunz K, Gerhardt S, Schüle R, Jung M, Einsle O, Günther S. (2013) 4-Acyl pyrroles: mimicking acetylated lysines in histone code reading. Angew. Chem. Int. Ed. Engl., 52 (52): 14055-9. [PMID:24272870]

8. McLure KG, Gesner EM, Tsujikawa L, Kharenko OA, Attwell S, Campeau E, Wasiak S, Stein A, White A, Fontano E et al.. (2013) RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. PLoS ONE, 8 (12): e83190. [PMID:24391744]

9. Mirguet O, Lamotte Y, Chung CW, Bamborough P, Delannée D, Bouillot A, Gellibert F, Krysa G, Lewis A, Witherington J et al.. (2014) Naphthyridines as novel BET family bromodomain inhibitors. ChemMedChem, 9 (3): 580-9. [PMID:24000170]

10. Seal J, Lamotte Y, Donche F, Bouillot A, Mirguet O, Gellibert F, Nicodeme E, Krysa G, Kirilovsky J, Beinke S et al.. (2012) Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A). Bioorg. Med. Chem. Lett., 22 (8): 2968-72. [PMID:22437115]

How to cite this page

Bromodomain kinase (BRDK) family: bromodomain containing 2. Last modified on 08/09/2015. Accessed on 19/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1944.