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bromodomain containing 4

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Target not currently curated in GtoImmuPdb

Target id: 1945

Nomenclature: bromodomain containing 4

Abbreviated Name: BRD4

Family: Bromodomain kinase (BRDK) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1362 19p13.12 BRD4 bromodomain containing 4
Mouse - 1400 17 17.39 cM Brd4 bromodomain containing 4
Rat - 1403 7 q11 Brd4 bromodomain containing 4
Previous and Unofficial Names Click here for help
CAP | chromosome-associated protein | HUNK1 | MCAP | Mitotic chromosome-associated protein
Database Links Click here for help
Alphafold O60885 (Hs), Q9ESU6 (Mm)
BRENDA 2.7.11.1
CATH/Gene3D 1.20.920.10
ChEMBL Target CHEMBL1163125 (Hs), CHEMBL3085619 (Mm)
Ensembl Gene ENSG00000141867 (Hs), ENSMUSG00000024002 (Mm), ENSRNOG00000006770 (Rn)
Entrez Gene 23476 (Hs), 57261 (Mm), 362844 (Rn)
Human Protein Atlas ENSG00000141867 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:23476 (Hs), mmu:57261 (Mm), rno:362844 (Rn)
OMIM 608749 (Hs)
Pharos O60885 (Hs)
RefSeq Nucleotide NM_058243 (Hs), NM_020508 (Mm), NM_001100903 (Rn)
RefSeq Protein NP_490597 (Hs), NP_065254 (Mm), NP_001094373 (Rn)
SynPHARM 79926 (in complex with BI-2536)
79910 (in complex with BzT-7)
79940 (in complex with compound 15 (Hay et al., 2013))
80625 (in complex with compound 1 [PMID: 25408830])
79912 (in complex with compound 4d [PMID: 21851057])
81940 (in complex with compound 7d [PMID: 25703523])
83518 (in complex with CPI-0610)
79909 (in complex with GW841819X)
79916 (in complex with I-BET151)
79904 (in complex with I-BET-762)
79939 (in complex with isoxazole azepine compound 3)
79900 (in complex with (+)-JQ1)
82041 (in complex with LY 294002)
79901 (in complex with MS417)
79898 (in complex with MS436)
79925 (in complex with PFI-1)
82686 (in complex with RVX 208)
79936 (in complex with XD1)
79935 (in complex with XD14)
UniProtKB O60885 (Hs), Q9ESU6 (Mm)
Wikipedia BRD4 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Bromo domain 1 in human Bromodomain Containing Protein 4 (BRD4)
PDB Id:  2OSS
Resolution:  1.35Å
Species:  Human
References:  11
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H4K5acK8ac)
PDB Id:  3UVW
Resolution:  1.37Å
Species:  Human
References:  11
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the first bromodomain of human BRD4 in complex with IBET-151.
PDB Id:  3ZYU
Ligand:  I-BET151
Resolution:  1.5Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human BRD4-BD1 in complex with the benzotriazepine ligand BzT-7
PDB Id:  3U5L
Ligand:  BzT-7
Resolution:  1.39Å
Species:  Human
References:  10
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the first bromodomain of human BRD4 in complex with a 2-amine-9H-purine ligand
PDB Id:  4XY9
Ligand:  compound 7d [PMID: 25703523]
Resolution:  1.83Å
Species:  Human
References:  27
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the second bromodomain of human BRD2 in complex with a quinazolinone ligand (RVX-208).
PDB Id:  4MR6
Ligand:  apabetalone
Resolution:  1.67Å
Species:  Human
References:  28
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the first bromodomain of human BRD4 bound to CPI-0610.
PDB Id:  5HLS
Ligand:  pelabresib
Resolution:  2.18Å
Species:  Human
References:  1
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ARV-771 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pKd 30
⤷ pKd 8.1 (Kd 7.6x10-9 M) [30]
Description: Binding affinity for bromodomain 2 of hBRD4.
MZ1 Small molecule or natural product Hs Binding 7.6 pKd 2
⤷ pKd 7.6 (Kd 2.6x10-8 M) [2]
Description: Binding affiniy for recombinant human Brd4 BD2 in vitro.
BI-2536 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKd 4
⤷ pKd 7.4 (Kd 3.7x10-8 M) [4]
Description: Assayed using recombinant BRD4-BD1.
(+)-JQ1 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pKd 12
⤷ pKd 7.3 (Kd 5x10-8 M) [12]
Description: Displacement binding constant to recombinant BRD4-BD1 protein.
GSK852 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 – 9.0 pKd 23
⤷ pKd 9.0 (Kd 1x10-9 M) [23]
Description: Binding affinity at BD2, determined by BROMOscan
pKd 5.5 (Kd 3.162x10-6 M) [23]
Description: Binding affinity at BD1, determined by BROMOscan
XD14 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKd 24
⤷ pKd 6.8 (Kd 1.6x10-7 M) [24]
Description: Assay using recombinant BRD4-BD1.
fedratinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKd 4
⤷ pKd 6.8 (Kd 1.64x10-7 M) [4]
BzT-7 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.2 pKd 10
⤷ pKd 6.2 (Kd 6.4x10-7 M) [10]
Description: Measuring the dissociation constant for the compound's interaction with BD1 of BRD4.
LY 294002 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pKd 8
⤷ pKd 5.7 (Kd 1.83x10-6 M) [8]
compound 7d [PMID: 25703523] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.3 pKd 27
⤷ pKd 5.3 (Kd 4.651x10-6 M) [27]
colchicine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.7 pKd 24
⤷ pKd 4.7 (Kd 2x10-5 M) [24]
XD1 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 4.3 pKd 24
⤷ pKd 4.3 (Kd 4.6x10-5 M) [24]
mivebresib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.5 – 8.9 pKi 33
⤷ pKi 8.5 – 8.9 (Ki 3.5x10-9 – 1.4x10-9 M) [33]
Description: Inhibition of binding to the BD1 (8.46) or BD2 (8.85) bromodomains of human BRD4 using a TR-FRET assay.
MS436 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.3 – 7.5 pKi 38
⤷ pKi 7.3 – 7.5 (Ki 5x10-8 – 3x10-8 M) [38]
Description: Range of inhibition of binding across both Brd1 and Brd2 bromodomains of BRD4.
molibresib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.2 pEC50 3
⤷ pEC50 6.2 (EC50 7x10-7 M) [3]
Description: Measured in a ApoA1 reporter gene assay.
BMS-986158 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.0 pIC50 14
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [14]
Description: Time-resolved FRET binding assay using hBRD4 BD-1 bromodomain.
NHWD-870 Small molecule or natural product Hs Inhibition 8.6 pIC50 36
⤷ pIC50 8.6 (IC50 2.72x10-9 M) [36]
Description: Inhibition of BRD4 (BD1 + BD2) by NHWD-870 in a biochemical assay.
dBET6 Small molecule or natural product Hs Inhibition 7.8 pIC50 35
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [35]
Description: Inhibition of BRD4 (BD1) kinase activity.
GW841819X Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 3
⤷ pIC50 7.8 (IC50 1.55x10-8 M) [3]
Description: Displacement of a tetra-acetylated histone H4 peptide from the tandem BET bromodomains of BRD4.
isoxazole azepine compound 3 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.6 pIC50 15
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [15]
Description: Assayed using recombinant BRD4-BD1.
compound 11h [PMID: 29808961] Small molecule or natural product Hs Inhibition 7.6 pIC50 21
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [21]
Description: Inhibition of BRD4(1).
dual BRD4/PLK1 inhibitor 23 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 22
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [22]
Description: Biochemical inhibition of BRD4-BD1.
MS417 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.5 pIC50 37
⤷ pIC50 7.5 (IC50 3x10-8 M) [37]
Description: Inhibition of MS417 binding to recombinant BRD4-BD1 using FITC-labeled MS417 as the assay probe.
molibresib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 3.61x10-8 M) [3]
Description: Displacement of a tetra-acetylated histone H4 peptide from the tandem BET bromodomains of BRD4.
CPI-203 Small molecule or natural product Hs Inhibition 7.4 pIC50 7
⤷ pIC50 7.4 (IC50 3.7x10-8 M) [7]
Description: Measured using a bead-based fluorescent proximity assay.
pelabresib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.4 pIC50 1
⤷ pIC50 7.4 (IC50 3.9x10-8 M) [1]
Description: IC50 vs. BRD4-BD1
compound 3 [PMID: 25408830] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 6
⤷ pIC50 7.1 (IC50 7.94x10-8 M) [6]
amredobresib Small molecule or natural product Hs Inhibition 7.1 pIC50 9
⤷ pIC50 7.1 (IC50 9x10-8 M) [9]
WNY0824 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 34
⤷ pIC50 7.0 (IC50 1.09x10-7 M) [34]
compound 2 [PMID: 25408830] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.7 pIC50 6
⤷ pIC50 6.7 (IC50 2x10-7 M) [6]
PFI-1 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.7 pIC50 13
⤷ pIC50 6.7 (IC50 2.2x10-7 M) [13]
Description: Assayed using recombinant BRD4-BD1.
XY-06-007 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 20
⤷ pIC50 6.6 (IC50 2.54x10-7 M) [20]
compound 38 [PMID: 24000170] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 26
⤷ pIC50 6.5 (IC50 3.16x10-7 M) [26]
compound 9 [PMID: 23517011] Small molecule or natural product Hs Inhibition 6.4 pIC50 18
⤷ pIC50 6.4 (IC50 3.71x10-7 M) [18]
Description: Measured using a bead-based fluorescent proximity assay assessing BRD4-BD1 interaction with acetylated histone.
compound 36 [PMID: 24000170] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 26
⤷ pIC50 6.2 (IC50 6.31x10-7 M) [26]
I-BET151 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pIC50 5
⤷ pIC50 6.1 (IC50 7.9x10-7 M) [5]
compound 15 [Hay et al., 2013] Small molecule or natural product Hs Inhibition 5.9 pIC50 17
⤷ pIC50 5.9 (IC50 1.258x10-6 M) [17]
compound 6 [PMID: 30125504] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.6 pIC50 22
⤷ pIC50 5.6 (IC50 2.579x10-6 M) [22]
Description: Biochemical inhibition of BRD4-BD1.
compound 4d [PMID: 21851057] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.3 pIC50 19
⤷ pIC50 5.3 (IC50 4.8x10-6 M) [19]
Description: Inhibition of binding to recombinant BRD4-BD1.
compound 1 [PMID: 25408830] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.1 pIC50 6
⤷ pIC50 4.1 (IC50 7.943x10-5 M) [6]
N-methyl-2-pyrrolidone Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 2.2 pIC50 31
⤷ pIC50 2.2 (IC50 6x10-3 M) [31]
Inhibitor Comments
Zhang et al. (2012) also report an IC50 for MS417 at BRD4-BD2 of 46nM [37].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
apabetalone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 pIC50 25
⤷ pIC50 7.4 (IC50 4x10-8 M) [25]
Description: Measured using a TR-FRET assay to evaluate binding to BD2 of BRD4.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0050727 regulation of inflammatory response IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050727 regulation of inflammatory response IDA
General Comments
BRD4 has been reported to act as an atypical kinase, phosphorylating Ser2 present in the C-terminal domain (CTD) of RNA polymerase II, highlighting a direct role of BRD4 in transcription [7]. In certain cancers aberrant BRD4 expression mediates carcinigogenesis by hyperacetylationg the chromatin of genes involved in promoting cell proliferation. As a result, BRD4 inhibitors (and inhibitors of other BET family proteins) are being developed and investigated for therapeutic anti-cancer potential [29,32].

SARS-CoV-2/COVID-19
Experimental in vitro evidence, using affinity-purification mass spectrometry (AP-MS), indicates a protein-protein interaction between BRD2/4 and the SARS-CoV-2 envelope protein (E) [16], although whether this interaction is realistic based on spatial distribution of the host and viral proteins within cells was not addressed in this study. Speculatively, BRD inhibitors such as JQ1 and RVX 208, or BRD degraders (PROTACs; e.g. dBET6 or MZ1) could be utilised to examine the effect of inhibiting the BRD2/4-E interaction on SARS-CoV-2 pathobiology.

References

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1. Albrecht BK, Gehling VS, Hewitt MC, Vaswani RG, Côté A, Leblanc Y, Nasveschuk CG, Bellon S, Bergeron L, Campbell R et al.. (2016) Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials. J Med Chem, 59 (4): 1330-9. [PMID:26815195]

2. Chan KH, Zengerle M, Testa A, Ciulli A. (2018) Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds. J Med Chem, 61 (2): 504-513. [PMID:28595007]

3. 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]

4. Ciceri P, Müller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, Lasater EA, Pallares G, Picaud S, Wells C et al.. (2014) Dual kinase-bromodomain inhibitors for rationally designed polypharmacology. Nat Chem Biol, 10 (4): 305-12. [PMID:24584101]

5. 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]

6. Demont EH, Bamborough P, Chung CW, Craggs PD, Fallon D, Gordon LJ, Grandi P, Hobbs CI, Hussain J, Jones EJ et al.. (2014) 1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain. ACS Med Chem Lett, 5 (11): 1190-1195. [PMID:25408830]

7. Devaiah BN, Lewis BA, Cherman N, Hewitt MC, Albrecht BK, Robey PG, Ozato K, Sims 3rd RJ, Singer DS. (2012) BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci USA, 109 (18): 6927-32. [PMID:22509028]

8. 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]

9. Engelhardt H, Gianni D, Smethurst C. (2016) Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors. Patent number: US9266891B2. Assignee: Boehringer Ingelheim International GmbH. Priority date: 16/11/2012. Publication date: 23/02/2016.

10. Filippakopoulos P, Picaud S, Fedorov O, Keller M, Wrobel M, Morgenstern O, Bracher F, Knapp S. (2012) Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family. Bioorg Med Chem, 20 (6): 1878-86. [PMID:22137933]

11. Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Müller S, Pawson T et al.. (2012) Histone recognition and large-scale structural analysis of the human bromodomain family. Cell, 149 (1): 214-31. [PMID:22464331]

12. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I et al.. (2010) Selective inhibition of BET bromodomains. Nature, 468 (7327): 1067-73. [PMID:20871596]

13. Fish PV, Filippakopoulos P, Bish G, Brennan PE, Bunnage ME, Cook AS, Federov O, Gerstenberger BS, Jones H, Knapp S et al.. (2012) Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem, 55 (22): 9831-7. [PMID:23095041]

14. Gavai AV, Fink BE, Fairfax DJ, Martin GS, Rossiter LM, Holst CL, Kim SH, Leavitt KJ, Mastalerz H, Han WC et al.. (2009) Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epidermal growth factor receptor 1 and 2 kinases. J Med Chem, 52 (21): 6527-30. [PMID:19821562]

15. Gehling VS, Hewitt MC, Vaswani RG, Leblanc Y, Côté A, Nasveschuk CG, Taylor AM, Harmange JC, Audia JE, Pardo E et al.. (2013) Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors. ACS Med Chem Lett, 4 (9): 835-40. [PMID:24900758]

16. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583 (7816): 459-468. [PMID:32353859]

17. Hay D, Fedorov O, Filippakopoulos P, Martin S, Philpott M, Picaud S, Hewings DS, Uttakar S, Heightman TD, Conway SJ et al.. (2013) The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains. Medchemcomm, 4 (1): 140-144.

18. Hewings DS, Fedorov O, Filippakopoulos P, Martin S, Picaud S, Tumber A, Wells C, Olcina MM, Freeman K, Gill A et al.. (2013) Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands. J Med Chem, 56 (8): 3217-27. [PMID:23517011]

19. 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]

20. Hu R, Wang WL, Yang YY, Hu XT, Wang QW, Zuo WQ, Xu Y, Feng Q, Wang NY. (2022) Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor. Eur J Med Chem, 227: 113922. [PMID:34700270]

21. Li X, Zhang J, Zhao L, Yang Y, Zhang H, Zhou J. (2018) Design, Synthesis, and in vitro Biological Evaluation of 3,5-Dimethylisoxazole Derivatives as BRD4 Inhibitors. ChemMedChem, 13 (13): 1363-1368. [PMID:29808961]

22. Liu S, Yosief HO, Dai L, Huang H, Dhawan G, Zhang X, Muthengi AM, Roberts J, Buckley DL, Perry JA et al.. (2018) Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors. J Med Chem, 61 (17): 7785-7795. [PMID:30125504]

23. Lucas SCC, Atkinson SJ, Chung CW, Davis R, Gordon L, Grandi P, Gray JJR, Grimes T, Phillipou A, Preston AG et al.. (2021) Optimization of a Series of 2,3-Dihydrobenzofurans as Highly Potent, Second Bromodomain (BD2)-Selective, Bromo and Extra-Terminal Domain (BET) Inhibitors. J Med Chem, 64 (15): 10711-10741. [PMID:34260229]

24. 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]

25. 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]

26. 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]

27. Picaud S, Strocchia M, Terracciano S, Lauro G, Mendez J, Daniels DL, Riccio R, Bifulco G, Bruno I, Filippakopoulos P. (2015) 9H-Purine Scaffold Reveals Induced-Fit Pocket Plasticity of the BRD9 Bromodomain. J Med Chem, 58 (6): 2718-36. [PMID:25703523]

28. Picaud S, Wells C, Felletar I, Brotherton D, Martin S, Savitsky P, Diez-Dacal B, Philpott M, Bountra C, Lingard H et al.. (2013) RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci USA, 110 (49): 19754-9. [PMID:24248379]

29. Pérez-Salvia M, Esteller M. (2017) Bromodomain inhibitors and cancer therapy: From structures to applications. Epigenetics, 12 (5): 323-339. [PMID:27911230]

30. Raina K, Lu J, Qian Y, Altieri M, Gordon D, Rossi AM, Wang J, Chen X, Dong H, Siu K et al.. (2016) PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proc Natl Acad Sci USA, 113 (26): 7124-9. [PMID:27274052]

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How to cite this page

Bromodomain kinase (BRDK) family: bromodomain containing 4. Last modified on 23/08/2022. Accessed on 09/12/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1945.