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 (298)
Related Products (298)
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PROTAC BRD4-DCAF1 degrader-1
0 ImagesCat. No.: HY-169151CAS No.: 3036944-87-0
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BRD4/FKBP12 ligand 1
0 ImagesCat. No.: HY-176477BRD4/FKBP12 ligand 1 is a heterobifunctional BRD4 and FKBP12 (Kd of 0.4 nM) ligand. BRD4/FKBP12 ligand 1 has positive cooperativity in BRD4 binding when pre-bound to FKBP12, and FKBP12-dependent cytotoxicity in cancer cells via the CellTrap effect. BRD4/FKBP12 ligand 1 can be used for the research of acute myeloid leukemia, multiple myeloma, prostate carcinoma.
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BRD4 ligand 14
0 ImagesCat. No.: HY-180152BRD4 ligand 14 (Compound Y47) is a BRD4 inhibitor. BRD4 ligand 14 exhibits mild anticancer properties against acute myeloid leukemia by inhibiting BRD4. BRD4 ligand 14 can also be used as a ligand for target protein for PROTAC in the development and design of PROTAC BRD4 degraders, such as PROTAC BRD4 Degrader-42 (HY-180150).
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BT-PROTAC
0 ImagesCat. No.: HY-155371CAS No.: 3032848-64-6BT-PROTAC is a bioorthogonally activatable BRD4/BRD3 PROTAC degrader prodrug. BT-PROTAC is inactive when present alone, but upon activation by tetrazine compounds, it promotes the degradation of BRD4 and BRD3 via the ubiquitin-proteasome system, inhibits c-Myc expression, activates caspase-3, and induces apoptosis in breast cancer cells. BT-PROTAC can be used for breast cancer research.
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PROTAC BRD4 Degrader-43
0 ImagesCat. No.: HY-181164PROTAC BRD4 Degrader-43 is a BRD4 PROTAC degrader. PROTAC BRD4 Degrader-43 recruits the DCAF1-DDB1-Cul4A E3 ligase complex via a Vpr-derived peptide moiety to induce BRD4 ubiquitination and degradation through the ubiquitin-proteasome system. PROTAC BRD4 Degrader-43 exhibits potent HIV latency-reversing activity. PROTAC BRD4 Degrader-43 can be used for the research of HIV-1 latent infection. (Pink: BRD4 ligand (HY-13030); Blue: Cul4A-DDB1-DCAF1 ligand (HY-P11640); Black: conjugate of PEG linker + cell-penetrating peptide (HY-P2483))
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Penipanoid C
0 ImagesCat. No.: HY-N16067CAS No.: 1442381-95-4Penipanoid C (Compound 9) is a BRD4 inhibitor. Penipanoid C can be isolated from marine sediment-derived fungus Penicillium paneum SD-44. Penipanoid C has anti-inflammatory activity and cytotoxic activity against the SMMC-7721 cells. Penipanoid C can be used for inflammatory diseases research.
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BRD4-BD1-IN-2
0 ImagesCat. No.: HY-143300CAS No.: 2761321-26-8
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FLT3/JAK2/BRD4 ligand-1
0 ImagesCat. No.: HY-175611CAS No.: 3067695-60-4
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BRD4 ligand 8
0 ImagesCat. No.: HY-174812BRD4 ligand 8 (Compound J558) is a BRD4 inhibitor. BRD4 ligand 8 can be used for synthesis of PROTAC BRD4 Degrader-33 (HY-174811).
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BRD4-IN-3
0 ImagesCat. No.: HY-104072CAS No.: 1380087-86-4BRD4-IN-3 (compound 141) is a potent BRD4 inhibitor with an IC50 of <0.5 µM. BRD4-IN-3 shows cytoxicity for MYC-Raji with an IC50 value of >1 µM.
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BRD4 ligand 15
0 ImagesCat. No.: HY-182371CAS No.: 3076613-24-3
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PROTAC BRD4 Degrader-22
0 ImagesCat. No.: HY-155393CAS No.: 3032850-37-3
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Hyp-dBET1
0 ImagesCat. No.: HY-173256Hyp-dBET1 is a hypoxia-activated BRD4 PROTAC degrader. The IC50 of Hyp-dBET1 for reducing cell viability under hypoxic conditions is approximately 153 nM to 192 nM, while it shows low activity under normoxic conditions (IC50 of approximately 2.8 μM to 3.8 μM). Hyp-dBET1 induces BRD4 degradation under hypoxic conditions, converts to dBET1 in hypoxic environments, and downregulates the expression level of ZFP-91. Hyp-dBET1 can be used in studies related to breast cancer, cervical cancer and solid tumors.
