BRD4
BRD4 (Bromodomain Containing Protein 4) is a member of the BET (bromodomain and extra-terminal) protein family that recognizes acetylated histones and functions as a central regulator of chromatin-associated transcriptional programs[1][2]. Mechanistically, BRD4 promotes RNA polymerase II transcriptional elongation through functional interaction with positive transcription elongation factor b (P-TEFb), thereby facilitating productive gene expression and transcriptional pause release[3][4][5]. Beyond transcriptional control, BRD4 contributes to chromatin organization, DNA replication, and DNA damage response pathways, linking epigenetic regulation to genome stability[1][6]. BRD4 also supports efficient transcription elongation that limits R-loop accumulation and transcription-replication conflicts, processes that are important for maintaining cellular viability[6]. In disease contexts, aberrant BRD4 activity has been associated with cancer, inflammatory disorders, viral infection, and neurological disease, reflecting its broad influence on gene regulatory networks[1][2]. In multiple tumor models, BRD4 regulates transcriptional programs linked to oncogenic drivers and tumor cell survival, supporting its relevance as a therapeutic target[7][8]. Compared with related BET family members BRD2, BRD3, and the testis-restricted BRDT, BRD4 possesses a characteristic C-terminal domain that mediates interaction with P-TEFb and plays a distinct role in transcriptional elongation control[3][9]. For experimental applications, small-molecule BET inhibitors such as JQ1 and I-BET disrupt bromodomain-dependent chromatin interactions and have become widely used tools for investigating BRD4-dependent transcriptional mechanisms and target validation in disease models[1][7][8].
References:
- [1]. Cheung KL, et al. The Functions of BET Proteins in Gene Transcription of Biology and Diseases. Front Mol Biosci. 2021 Sep 3;8:728777. [Content Brief]
- [2]. Liang Y, et al. BRD4 in physiology and pathology: ''BET'' on its partners. Bioessays. 2021 Dec;43(12):e2100180. [Content Brief]
- [3]. Zheng B, et al. Distinct layers of BRD4-PTEFb reveal bromodomain-independent function in transcriptional regulation. Mol Cell. 2023 Aug 17;83(16):2896-2910.e4. [Content Brief]
- [4]. Altendorfer E, et al. BRD4: a general regulator of transcription elongation. Transcription. 2022 Feb-Jun;13(1-3):70-81. [Content Brief]
- [5]. Kanno T, et al. BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones. Nat Struct Mol Biol. 2014 Dec;21(12):1047-57. [Content Brief]
- [6]. Edwards DS, et al. BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation. Cell Rep. 2020 Sep 22;32(12):108166. [Content Brief]
- [7]. Jung M, et al. Targeting BET bromodomains for cancer treatment. Epigenomics. 2015;7(3):487-501. [Content Brief]
- [8]. Lucas X, et al. 4-Acyl pyrroles: mimicking acetylated lysines in histone code reading. Angew Chem Int Ed Engl. 2013 Dec 23;52(52):14055-9. [Content Brief]
- [9]. Kargbo RB. PROTAC Degradation of Bromodomain for the Treatment of Hyperplasia and Cancer. ACS Med Chem Lett. 2019 Sep 30;10(10):1372-1373. doi: 10.1021/acsmedchemlett.9b00424. PMID: 31620218; PMCID: PMC6792170. et al. PROTAC Degradation of Bromodomain for the Treatment of Hyperplasia and Cancer. ACS Med Chem Lett. 2019 Sep 30;10(10):1372-1373. [Content Brief]
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BRD4 Related Products (285)
Related Products (285)
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ABBV-744
0 ImagesABBV-744 is a first-in-class, orally active and selective inhibitor of the BDII domain of BET family proteins with IC50 values ranging from 4 to 18 nM for BRD2, BRD3, BRD4 and BRDT. ABBV-744 is primarily metabolized by CYP3A4 with agent-like properties enable the investigation of its antitumor efficacy and tolerability.
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BRD4 degrader-3
0 ImagesBRD4 degrader-3 is a potent bromodomain BRD4 degrader extracted from patent WO2020055976A1, example 1a, has IC50s of 15.5 and 12.3 nM for BRD4-BD1 and BRD4-BD2, respectively. PROTAC BRD4 Degrader-7 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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MMH1
0 ImagesMMH1 is a novel BRD4 molecular glue degrader. MMH1 functions by recruiting the CUL4 DCAF16 ligase to the second bromodomain of BRD4 (BRD4 BD2). MMH1 binds to the JQ1-binding site of BRD4 BD2, acts as a template to covalently modify Cys58 of DCAF16, stabilizes the BRD4-DCAF16 ternary complex, and thereby promotes BRD4 degradation via the CRL4DCAF16 ubiquitin ligase pathway. Using BRD4 BD2 as a structural template, MMH1 covalently modifies Cys87 of GAK and induces the GAK-BRD4 BD2 interaction. Through its covalent mechanism, MMH1 exhibits sustained BRD4 degradation activity, and shows selective degradation activity for BRD4 BD2 over BRD4 BD1.
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Zavabresib
0 ImagesSynonyms: OPN-2853; PLX2853; BET-IN-16Zavabresib (OPN-2853; PLX2853; BET-IN-16) is an orally active inhibitor of the BET family of proteins. Zavabresib blocks bromodomain-mediated interactions, reduces BRD4 enrichment at the regulatory regions of transcription factors in T cells, exerts tumor growth inhibitory effects, and enhances the efficacy of immunotherapy. Zavabresib is applicable to research on chronic lymphocytic leukemia, castration-resistant prostate cancer, diffuse large B-cell lymphoma, colon adenocarcinoma, and myelofibrosis.
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Pelabresib
0 ImagesSynonyms: CPI-0610Pelabresib (CPI-0610) is a potent, selective, orally active and cell-active BET inhibitor. Pelabresib inhibits BRD4-BD1 with an IC50 of 39 nM, and with an EC50 value of 0.18 μM for MYC.
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Mivebresib
0 ImagesSynonyms: ABBV-075Mivebresib (ABBV-075) is a potent and orally active bromodomain and extraterminal domain (BET) bromodomain inhibitor. Mivebresib binds to BRD4 with a Ki of 1.5 nM.
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GNE-987
0 ImagesGNE-987 is a VHL-dependent BRD4 PROTAC degrader. GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50=0.03 nM for EOL-1 AML cell line). GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50=4.7 and 4.4 nM, respectively). GNE-987 can be used for the research of cancer.
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GSK778
0 ImagesSynonyms: iBET-BD1GSK778 (iBET-BD1), a chemical probe, is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models.
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CPI-637
0 ImagesCPI-637 is a selective and potent CBP/EP300 bromodomain inhibitor with IC50 values of 0.03 μM, 0.051 μM and 11.0 μM for CBP, EP300 and BRD4 BD-1, respectively, and an EC50 of 0.3 μM for CBP.
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AR/BRD4 RIPTAC-1
0 ImagesCat. No.: HY-176521CAS No.: 3083307-42-7AR/BRD4 RIPTAC-1 (Compound II-5) is an orally active Regulatory-inducible proximity-targeting chimera (RIPTAC). AR/BRD4 RIPTAC-1 induces the formation of a stable ternary complex between the androgen receptor (AR) and BRD4, thereby blocking BRD4 function. AR/BRD4 RIPTAC-1 inhibits the growth and proliferation of tumor cells. AR/BRD4 RIPTAC-1 holds promise for use in prostate cancer research.
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FKBP12 PROTAC dTAG-7
0 ImagesSynonyms: dTAG-7FKBP12 PROTAC dTAG-7 (dTAG-7) is a FKBP12F36V PROTAC degrader. FKBP12 PROTAC dTAG-7 binds FKBP12F36V and CRBN to form a complex, mediating degradation via the ubiquitin-proteasome system. FKBP12 PROTAC dTAG-7 mediates the degradation of FKBP12F36V-tagged nuclear and cytoplasmic proteins, including BRD4, HDAC1, EZH2, MYC, PLK1, KRASG12V, and antigen fusion proteins. FKBP12 PROTAC dTAG-7 enhances MHC class I antigen presentation. FKBP12 PROTAC dTAG-7 is applicable to leukemia-related research.
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BRD4 degrader AT1
0 ImagesBRD4 degrader AT1 is a selective PROTAC BRD4 degrader. BRD4 degrader AT1 induces depletion of Brd4 protein in cells. BRD4 degrader AT1 exhibits highly selective depletion of Brd4 over Brd2 and Brd3 in cells.
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GSK046
0 ImagesSynonyms: iBET-BD2GSK046 (iBET-BD2), a chemical probe, is a potent, selective and orally active BD2 bromodomain inhibitor of the BET proteins, with IC50s of 264 nM (BRD2 BD2), 98 nM (BRD3 BD2), 49 nM (BRD4 BD2) and 214 nM (BRDT BD2), respectively. GSK046 has immunomodulatory activity.
