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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BRD4-IN-42
0 ImagesCat. No.: HY-184339BRD4-IN-42 is a BRD4 BD1 inhibitor with an IC50 of 108.50 nM. BRD4-IN-42 can be used for the synthesis of PROTACs and serves as the target protein moiety of PROTAC BET Degrader-18 (HY-184335). BRD4-IN-42 inhibits the proliferation of wild-type and SHP099-resistant acute myeloid leukemia cells. BRD4-IN-42 is applicable to research related to acute myeloid leukemia.
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CK2-TN03
0 ImagesCK2-TN03 is an ATP-competitive casein kinase 2 (CK2) inhibitor, with an IC50 of 165 nM and a Ki of 20 nM. CK2-TN03 inhibits CK2-mediated survivin activation and reduces CK2-dependent phosphorylation levels of BRD4/MYCN and AKT1. CK2-TN03 exerts anti-neuroblastoma effects by inhibiting survivin, leading to mitotic catastrophe and apoptosis of cancer cells. CK2-TN03 can be used in studies related to neuroblastoma.
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GXF-111
0 ImagesCat. No.: HY-153414GXF-111 is a BRD3 and BRD4-L PROTAC degrader. Its BD1 and BD2 Ki values against human BRD3 are 11.97 nM and 2.45 nM, respectively. The degradation activity of GXF-111 depends on its binding to BET proteins and Cereblon, as well as the involvement of a functional proteasome. The degradation selectivity of GXF-111 is mainly determined by differences in degradation kinetics and cell types. GXF-111 induces G1 phase cell cycle arrest, downregulates c-Myc expression, upregulates p21 expression, and exhibits antiproliferative activity against a variety of cancer cell lines. GXF-111 can serve as a research tool for cancer-related studies.
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BRD4 ligand 16
0 ImagesCat. No.: HY-184874CAS No.: 3032781-39-5BRD4 ligand 16 is a BRD4 ligand. BRD4 ligand 16 can serve as a ligand for the target protein in the synthesis of BRD4 PROTAC degraders, such as PROTAC BRD4 Degrader-17 (HY-143328). BRD4 ligand 16 is suitable for use in cancer research.
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DW34
0 ImagesCat. No.: HY-173564CAS No.: 2758171-54-7DW34 is an orally active pan-BRD4-D1 biased inhibitor with additional BRD4-D2 inhibitive activity. DW34 displays comparable inhibitive efficacy to I-BET151 (HY-13235) (EC50 = 0.16 μM) with low nanomolar EC50 values of 0.14 μM. DW34 significantly reduces liver inflammation induced by LPS (HY-D1056) and APAP (HY-66005) via reducing chemokine expression and cellular necrosis.
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CN427
0 ImagesCat. No.: HY-125230CAS No.: 2260887-54-3
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JY-21
0 ImagesCat. No.: HY-174975JY-21 is a BRD4 PROTAC degrader active against both long and short BRD4 isoforms. JY-21 binds to TRIM28, RACK1, LMO7 and FUS to induce proteasomal degradation of BRD4 isoforms (DC50: 5.944 μM for long BRD4 isoform; 3.797 μM for short BRD4 isoform). JY-21 is applicable to research related to triple-negative breast cancer.
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ZD-1-186
0 ImagesCat. No.: HY-180886ZD-1-186 is a non-degradative, covalent-dependent molecular glue that targets BCL6 and BRD9. ZD-1-186 inhibits the transcriptional output of MYC, relieves the repression of canonical BCL6 target loci (including CDKN1A (p21)), and mediates the selective recruitment of BRD9 to BCL6. ZD-1-186 can be used for research on diffuse large B-cell lymphoma.
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CFT-743
0 ImagesCat. No.: HY-182577CAS No.: 2154350-81-7CFT-743, a PROTAC-based heterobifunctional degrader and BET inhibtor, is a degrader of BRD4 bromodomain 1 (BD1) with a DC50 of 4.3 nM. CFT-743's antitumor activitiy is dependent on BET degradation and can be attenuated by Pomalidomide (HY-10984), which is a CRBN binding molecule. CFT-743 induces ubiquitination of BRD4 BD1. CFT-743 can be used for cancer research.
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PROTAC BRD4 Degrader-15
0 ImagesCat. No.: HY-139294CAS No.: 2417370-67-1PROTAC BRD4 Degrader-15 is a BRD4 PROTAC degrader with a DC50 of 2.1 nM. PROTAC BRD4 Degrader-15 forms a ternary complex with BRD4 and VHL ubiquitin ligase to induce degradation. PROTAC BRD4 Degrader-15 inhibits the transcription level of the MYC gene. PROTAC BRD4 Degrader-15 suppresses human megakaryocytopoiesis and exhibits antigen-dependent tumor growth inhibition in xenograft models of prostate cancer and acute myeloid leukemia. PROTAC BRD4 Degrader-15 can be used in studies related to prostate cancer and acute myeloid leukemia.
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PLX-4104
0 ImagesCat. No.: HY-182912CAS No.: 2851986-77-9PLX-4104 is an orally active BRD4 molecular glue degrader with a DC50 of 2 nM. PLX-4104 selectively promotes BRD4 degradation via DCAF11 recruitment, triggering ubiquitination and proteasomal breakdown. PLX-4104 inhibits cancer cell proliferation. PLX-4104 induces complete regression of AML xenograft tumors. PLX-4104 can be used for the research of acute myeloid leukemia.
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(S)-GNE-987
0 ImagesCat. No.: HY-129937CAS No.: 2738533-33-8(S)-GNE-987 is an isomer of GNE-987 (HY-129937A), which loses VHL binding capacity and BRD4 protein degradation activity, but retains BRD4 inhibitory activity. (S)-GNE-987 is a BRD4/BET inhibitor that potently binds to the BD1 and BD2 bromodomains of BRD4, with a BRD4 BD1 IC50 of 4.0 nM and a BRD4 BD2 IC50 of 3.9 nM. (S)-GNE-987 inhibits MYC expression and exhibits inhibitory activity against acute myeloid leukemia cells, whereas its CLL1‑6 antibody-drug conjugate shows almost no in vivo antitumor efficacy in the HL‑60 xenograft tumor model. (S)-GNE-987 can be used in related research on acute myeloid leukemia.
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PARP1/BRD4-IN-3
0 ImagesCat. No.: HY-169170PARP1/BRD4-IN-3 (compound HF4) is a potent BRD4 and PARP1 inhibitor with IC50 values of 1210, 2019 nM for BRD4, PARP1, respectively. PARP1/BRD4-IN-3 shows antiproliferative activities. PARP1/BRD4-IN-3 induces apoptosis and cell cycle arrest at G0/G1 phase. PARP1/BRD4-IN-3 causes DNA damage and reduces the protein expression of Rad51. PARP1/BRD4-IN-3 shows antitumor efficacy.
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BRD4 Inhibitor-29
0 ImagesCat. No.: HY-157460CAS No.: 902563-50-2BRD4 Inhibitor-29 (SQ-17) is a BRD4 inhibitor, with an IC50 of <100 nM. BRD4 Inhibitor-29 shows antiproliferative effect against prostate cancer cells.
