Bromodomains

Bromodomains (BRDs) are epigenetic "reader" domains that selectively recognize acetylated lysine (Kac) residues on the tails of histone proteins, and are the only known protein modules that can target acetylated lysine residues.

Products
Background
Literature (6)
Gene Data

Bromodomain Inhibitors

Cat. No. Product Name / Activity
5970 BAY 299
Potent and selective BRD1 and TAF1 inhibitor
5266 BAZ2-ICR
Selective BAZ2 inhibitor
5590 BI 9564
Potent and selective BRD9 and BRD7 inhibitor; orally active
4758 Bromosporine
Broad spectrum bromodomain inhibitor
7139 CeMMEC1
TAF1 inhibitor
5331 CPI 203
BET bromodomain inhibitor; arrests cell cycle at G1 phase
5635 GSK 2801
Selective BAZ2A and BAZ2B inhibitor
5385 GSK 5959
Potent and selective BRPF1 inhibitor
6198 GSK 6853
Potent and selective BRPF1 inhibitor
4650 I-BET 151 dihydrochloride
BET bromodomain inhibitor; also promotes differentiation of hiPSCs into megakaryocytes
6521 I-BET 762
Potent and high affinity BET bromodomain inhibitor; anti-inflammatory; orally bioavailable.
5591 I-BRD9
Potent and selective BRD9 inhibitor
4891 I-CBP 112
Selective CBP/p300 BRD inhibitor
7458 iBET-BD2
Potent and selective pan-BD2 inhibitor; orally bioavailable
4695 Ischemin sodium salt
CBP inhibitor; cell permeable
4499 (+)-JQ1
Potent and selective BET bromodomain inhibitor; cell permeable
6251 L Moses dihydrochloride
High affinity and selective PCAF bromodomain inhibitor
6068 Lin28 1632
Bromodomain inhibitor; also RNA binding protein Lin28 inhibitor and promotes mESC differentiation
5496 LP 99
Selective BRD7 and BRD9 inhibitor
2418 LY 303511
BRD2, BRD3 and BRD4 inhibitor; also negative control of LY 294002
5173 MS 436
Potent and selective BRD4(1) inhibitor
5546 NI 57
Potent and selective BRPF bromodomain inhibitor
5744 NVS-CECR2-1
Potent and selective CECR2 inhibitor
5289 OF 1
Selective BRPF1B and BRPF2 inhibitor
6181 OTX 015
BET bromodomain inhibitor; orally bioavailable
4928 OXF BD 02
Selective BRD4(1) inhibitor
4445 PFI 1
BET bromodomain inhibitor
5072 PFI 3
Potent and selective SMARCA2/4 and polybromo 1 inhibitor
5576 PFI 4
Potent and selective BRPF1B bromodomain inhibitor
7460 SGC SMARCA-BRDVIII
Potent and selective SMARCA2/4 and PB1(bromo 5)-selective SWI/SNF bromodomain inhibitor
4889 SGC-CBP30
Potent CBP/p300 BRD inhibitor
6670 TP 238
CECR2 and BPTF/FALZ inhibitor
6000 TP 472
Potent BRD9/7 inhibitor
4132 XMD 8-92
BRD4 inhibitor; also ERK5/BMK1 inhibitor

Degraders

Cat. No. Product Name / Activity
7256 ARV 771
Potent BET bromodomain PROTAC®; also degrades BRD-tagged chimeric antigen receptors (CAR) in T cells
6356 AT 1
(+)-JQ1 based PROTAC® with selectivity for BRD4
7319 BRD PHOTAC-I-3
Photoswitchable BET bromodomain degrader (PHOTAC)
7433 cis-SIM1
Negative control for SIM1 (Cat. No. 7432)
6327 dBET1
(+)-JQ1 based Degrader targeting BET bromodomains, active in vivo
6945 dBET6
Potent and selective (+)-JQ1 based Degrader targeting BET bromodomains, active in vivo
6606 dBRD9
Potent and selective BRD9 Degrader
6943 dBRD9-A
Potent BRD9 Degrader
6154 MZ 1
Selective BRD4 Degrader
6936 VZ 185
Potent and selective BRD7/9 Degrader
6713 ZXH 3-26
Potent and selective BRD4 Degrader

Controls

Cat. No. Product Name / Activity
6155 cis MZ 1
Negative Control for MZ 1 (Cat. No. 6154)
6939 cis-VZ 185
Negative control for VZ 185 (Cat. No. 6936)
5497 ent-LP 99
Negative Control for LP 99
6203 GSK 9311 hydrochloride
Negative control for GSK 6853
5603 (-)-JQ1
Negative control for (+)-JQ1
5999 TP 472N
Negative control for TP 472

Other

Cat. No. Product Name / Activity
6588 (+)-JQ1 carboxylic acid
Carboxylic acid-functionalized BET bromodomain inhibitor
6589 (+)-JQ1 PA
Functionalized BET bromodomain inhibitor; 'click' ligand for PROTACs

Bromodomain Structure and Function

There are approximately 61 unique human Bromodomains. These protein modules have been identified 42 proteins with diverse functions from the histone acetyltransferase (HAT) PCAF, which adds acetyl groups to lysine residues on histone tails, to the ATP-dependent helicase SNF2L2. This diversity has made it difficult to characterize the function of a given BRD-containing protein, particularly as some proteins may contain one or more additional epigenetic "reader" domains.

Structurally, bromodomains comprise four α-helices, designated A, B, C and Z, and two loops of different lengths, ZA and BC, forming a hydrophobic pocket that recognizes acetyl lysine (Figure 1). Bromodomains are grouped into eight families based on structure: BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9 and BRDT.

Bromodomain-containing proteins have an important role in controlling gene expression via remodeling of chromatin, histone modification and recognition and regulation of transcriptional machinery.

BET Bromodomains

Of particular interest is the BET (bromodomain and extra-terminal) bromodomain family, which comprises the ubiquitously expressed proteins BRD2, BRD3, BRD4; and the testis-specific protein, BRDT. BET bromodomains are important in cellular differentiation and proliferation processes, and are characterized by having two distinct histone acetyl-lysine binding sites, denoted BD1 and BD2. BET proteins are key regulators of oncogenic transcription factors, such as MYC.

BRD4 BET bromodomain mode of action

Figure 1: Schematic showing the structure of bromodomains and the recognition of the acetylated lysine residues (Kac) on histone proteins by BRD4. The right-hand image highlights how bromodomain inhibitors, such as (+)-JQ1, block the binding of BRD4 to Kac.

Bromodomains and Disease

Bromodomains have been implicated in diseases such as cancer and inflammation. In cancer, bromodomain-containing proteins are often deregulated. In addition, mutations in the bromodomains themselves are frequently identified in a variety of cancers. Tumorigenesis and proliferation have been shown to be associated with deregulation of histone acetylation, which drives aberrant expression of growth and survival-promoting genes.

BRD4 is of interest as a therapeutic target for cancer, as a result of its binding to transcriptional sites of genes expressed during the M/G1 cell cycle transition. BRD4 has also been implicated in a rare but lethal form of cancer, NUT midline carcinoma (NUC), which is caused by a rearrangement of the nuclear protein in testis gene (NUT), causing the formation of a BRD4-NUT fusion gene.

In addition, BRD4 has been reported to function as a coactivator for the transcriptional activation of NFκB, which is implicated in the transcriptional control of inflammatory genes. Evidence suggests that BRD4 also plays a significant role in cardiovascular diseases, such as ischemic heart disease, hypertension, and cardiac hypertrophy, neurological disorders and respiratory conditions. BRD4 is also of interest in coronavirus infections, including COVID-19, as it is involved in transcriptional regulation of ACE2 and TMPRSS2, the host proteins that mediate viral cell entry.

Bromodomain Inhibitors and Their Uses

Bromodomain inhibitors such as the BET-selective bromodomain inhibitor (+)-JQ1 (Cat. No. 4499) have been valuable tools for elucidating the functions of bromodomains. In addition, BD1/BD2 selective inhibitors have enabled investigation of the functional activities of the individual binding sites. More recently protein Degraders (aka PROTAC® molecules) have been developed that selectively degrade a bromodomain of interest and allow exploration of the downstream consequences of protein knockdown. For example, MZ 1 (Cat. No. 6154) a PROTAC based on (+)-JQ1, brings about the selective degradation of BRD4 via the proteasome.

Genes regulated by BET are important in controlling cell identity. BRD4 is associated with control of pluripotency genes and maintaining the identity of embryonic stem cells. BET bromodomain inhibitors such as (+)-JQ1 and I-BET-151 (Cat. No. 4650) have been used in stem cell reprogramming protocols.

Bromodomain inhibitors have potential as cancer therapies and are the subject of clinical trials for a range of both solid and hematological tumors. Bromodomain Degraders are also in clinical trials for cancer.

PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.

Literature for Bromodomains

Tocris offers the following scientific literature for Bromodomains to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


Cancer Research Product Guide

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Stem Cell Research Product Guide

Stem Cell Research Product Guide

This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

  • Self-renewal and Maintenance
  • Differentiation
  • Reprogramming
  • Organoid Generation
  • GMP and Ancillary Material Grade Products
Epigenetics Scientific Review

Epigenetics Scientific Review

Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.

Epigenetics Research Bulletin

Epigenetics Research Bulletin

Produced by Tocris and updated in 2014, the epigenetics research bulletin gives an introduction into mechanisms of epigenetic regulation, and highlights key Tocris products for epigenetics targets including:

  • Bromodomains
  • DNA Methyltransferases
  • Histone Deacetylases
  • Histone Demethylases
  • Histone Methyltransferases
Epigenetics in Cancer Poster

Epigenetics in Cancer Poster

Adapted from the 2015 Cancer Product Guide Edition 3, this poster summarizes the main epigenetic targets in cancer. The dysregulation of epigenetic modifications has been shown to result in oncogenesis and cancer progression. Unlike genetic mutations, epigenetic alterations are considered to be reversible and thus make promising therapeutic targets.

Rheumatoid Arthritis Poster

Rheumatoid Arthritis Poster

Rheumatoid arthritis (RA) is a chronic destructive inflammatory autoimmune disease that results from a breakdown in immune tolerance, for reasons that are as yet unknown. This poster summarizes the pathology of RA and the inflammatory processes involved, as well as describing some of the epigenetic modifications associated with the disease and the potential for targeting these changes in the discovery of new treatments.

Bromodomain Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
BRD2 Human BRD2 NM_001113182 P25440
Mouse Brd2 NM_001204973 Q7JJ13
Rat Brd2 NM_212495 Q6MGA9
BRD3 Human BRD3 NM_007371 Q15059
Mouse Brd3 NM_023336 Q8K2F0
Rat Brd3 NM_001108575 NP_001102045
BRD4 Human BRD4 NM_058243 O60885
Mouse Brd4 NM_020508 Q9ESU6
Rat Brd4 NM_001100903 NP_001094373
BRDT Human BRDT NM_207189 Q58F21
Mouse Brdt NM_054054 Q91Y44
Rat - - -