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 (300)
Related Products (300)
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ZnPc-O3-JQ1
0 ImagesCat. No.: HY-176724ZnPc-O3-JQ1 is a photoactivatable BRD4-targeting degrader and photosensitizer, composed of monosubstituted amino zinc phthalocyanine (ZnPc), the BRD4 ligand JQ1, and a PEG linker. Upon activation by light, ZnPc-O3-JQ1 generates reactive oxygen species (ROS) and induces BRD4 degradation in an E3 ubiquitin ligase-independent manner. BRD4 degradation further reduces HIF-1α and GCL levels and restricts the SLC7A11/GSH-related antioxidant response, thereby enhancing photodynamic therapy-associated oxidative stress. ZnPc-O3-JQ1 can be used in research related to bladder cancer.
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HRG038
0 ImagesCat. No.: HY-176070HRG038 is a covalent CUL4DCAF16-base PROTAC-liked BRD4 degrader. HRG038 induces proteasome- and Cullin E3 ligase-dependent degradation, covalently targets cysteine residue C173 on DCAF16 to mediate BRD4 degradation, and induces reduction in BRD3 levels. HRG038 shows selective loss of the short BRD4 isoform over the long isoform in non-cancer cells, degrades both BRD4 isoforms in breast cancer cells, and does not impair cell viability in non-cancer cells. HRG038 can be used for the research of breast cancer.
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GSK785
0 ImagesCat. No.: HY-181003CAS No.: 3125088-67-4
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BRD4 degrader-6
0 ImagesCat. No.: HY-173327CAS No.: 3055207-38-7BRD4 degrader-6 is a dimeric BDR4 PROTAC degrader (DC50: < 0.1 μM). BRD4 degrader-6 promotes the ubiquitination and degradation of BDR4 and has anticancer activity.
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BET-IN-30
0 ImagesCat. No.: HY-181735BET-IN-30 (Compound 11d) is a BTE family protein inhibitor, which can act as a BRD2/BRD3/BRD4 target protein ligand and be used for the synthesis of PROTACs, such as PROTAC BET Degrader-15 (HY-181729). BET-IN-30 exhibits potent anti-proliferative activity against acute myeloid leukemia (AML) cells such as MV4-11. BET-IN-30 can be used for the study of AML.
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SJH1-51B
0 ImagesCat. No.: HY-162240SJH1-51B is a SKP1-recruiting BRD4 PROTAC degrader. SJH1-51B binds to SKP1 in the SKP1-FBXO7-CUL1-RBX1 complex, but shows no or weak binding to monomeric SKP1. SJH1-51B induces proteasome- and SKP1-dependent degradation of BRD4, and this degradation process relies on the neddylation modification of Cullin-RING E3 ligase. SJH1-51B induces proteasome-mediated degradation of the short isoform of BRD4 in non-cancer cells, while it induces proteasome-mediated degradation of both the long and short isoforms of BRD4 in breast cancer cells. SJH1-51B can be used for breast cancer research.
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PROTAC BRD2/BRD4 degrader-1
0 ImagesCat. No.: HY-130612CAS No.: 2570470-42-5PROTAC BRD2/BRD4 degrader-1 (compound 15) is a potent and selective BET protein BRD4 and BRD2 degrader, connected by ligands for Cereblon and BET. PROTAC BRD2/BRD4 degrader-1 rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 and BRD2 over BRD3. PROTAC BRD2/BRD4 degrader-1 effectively inhibits solid tumors with low cytotoxic effect.
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PROTAC BRD4 Degrader-33
0 ImagesCat. No.: HY-174811PROTAC BRD4 Degrader-33 is a BRD4 PROTAC degrader that recruits CRBN. PROTAC BRD4 Degrader-33 downregulates PD-L1 expression, inhibits tumor cell proliferation and tumor growth in mice by inducing ubiquitination and proteasomal degradation of BRD4. PROTAC BRD4 Degrader-33 can be used in the research of breast cancer.
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PROTAC BRD4 Degrader-21
0 ImagesCat. No.: HY-156566CAS No.: 2503036-46-0PROTAC BRD4 Degrader-21 is a BRD4-targeting PROTAC degrader with an IC50 value of 59 nM. PROTAC BRD4 Degrader-21 induces ubiquitination of BRD4, leading to its degradation via the proteasome. PROTAC BRD4 Degrader-21 binds to recombinant HSP90α protein with moderate affinity, having an IC50 of 100-1000 nM. PROTAC BRD4 Degrader-21 induces cancer cell death. PROTAC BRD4 Degrader-21 inhibits tumor growth in xenograft mouse models. PROTAC BRD4 Degrader-21 can be used for the research of acute myeloid leukemia, diffuse large B-cell lymphoma.
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BRD4 ligand 17
0 ImagesCat. No.: HY-116356CAS No.: 1629730-92-2
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BRD-SF2
0 ImagesCat. No.: HY-161368CAS No.: 3050690-26-8BRD-SF2 is a BRD4-targeted PROTAC degrader (DC50: 17.2 μM) (Blue: VHL ligand, black: linker, pink: BRD4 ligand).
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GXH-II-052
0 ImagesCat. No.: HY-150684CAS No.: 3031654-49-3GXH-II-052 is a potent bivalent bromodomain and extraterminal domain (BET) inhibitor. GXH-II-052 shows binding potential for BRD4-1, BRD4-2, BRD4-T, BRDT-1, BRDT-2, BRDT-T with Kd values of 28, 9.1, 4.8, 0.6, 8.4, 2.6 nM, respectively. GXH-II-052 shows antiproliferative activity. GXH-II-052 decreases the expression of c-Myc.
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PI3Kδ/BET-IN-1
0 ImagesCat. No.: HY-172130CAS No.: 3054869-10-9PI3Kδ/BET-IN-1 (compound 10b) shows excellent and balanced activities against PI3Kδ (IC50 = 112 nM) and BRD4-BD1 (IC50 = 19 nM) and exhibits strong antiproliferative activities in DLBCL cells.
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PROTAC BRD4 Degrader-48
0 ImagesCat. No.: HY-184923PROTAC BRD4 Degrader-48 is a BRD4 degrader with a Kd of 0.69 μM for human BRD4 and a DC50 of 0.21 μM. PROTAC BRD4 Degrader-48 binds to BRD4 and GID4 to form a ternary complex, and induces ubiquitination and degradation of BRD4 via the ubiquitin-proteasome pathway. PROTAC BRD4 Degrader-48 inhibits proliferation and migration of tumor cells, blocks tumor growth, and maintains degrading activity even in VHL- and CRBN-deficient models. PROTAC BRD4 Degrader-48 can be used in studies related to renal cell carcinoma.
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KB-0118
0 ImagesCat. No.: HY-176535CAS No.: 2648377-08-4Synonyms: BBC0115KB-0118 (BBC0115) is an orally active BET bromodomain inhibitor. KB-0118 selective binds to BRD2 and BRD4 over BRD3, with Kd values of 36.7 μM for BRD2 BD1 and 47.4 μM for BRD4 BD1. KB-0118 inhibits pro-inflammatory cytokines, including TNF, IL-1β, and IL-23a and selectively suppresses Th17 cell differentiation. KB-0118 modulates Th17-driven inflammation occurs through epigenetic suppression of BRD4, confirmed by downregulation of STAT3 and BRD4 target genes. KB-0118 has immunomodulatory effects in inflammatory bowel disease (IBD) model.
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BRD4/FKBP12 ligand 2
0 ImagesCat. No.: HY-176476BRD4/FKBP12 ligand 2 is a heterobifunctional BRD4 and FKBP12 (Kd of 1.0 nM) ligand. BRD4/FKBP12 ligand 2 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 2 can be used for the research of hematopoietic malignancy, multiple myeloma, prostate carcinoma, acute myeloid leukemia.
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PROTAC CBP/p300/BRD4 Degrader-1
0 ImagesCat. No.: HY-181758CAS No.: 3109024-12-3PROTAC CBP/p300/BRD4 Degrader-1 is a dual-target PROTAC degrader with DC50 values of 8.8 pM (BRD4), 6.55 nM (CBP), and 1.05 nM (p300). PROTAC CBP/p300/BRD4 Degrader-1 induces CRBN- and proteasome-dependent degradation of BRD4 and CBP/p300, downregulates c-Myc and acetyl-H3K27, induces apoptosis. PROTAC CBP/p300/BRD4 Degrader-1 acts as an antiproliferative and antitumor agent, induces tumor growth inhibition in xenograft models. PROTAC CBP/p300/BRD4 Degrader-1 can be used for the research of prostate cancer and colorectal cancer.
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PARP1/BRD4-IN-1
0 ImagesCat. No.: HY-144338CAS No.: 2758117-74-5
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NC-III-49-1
0 ImagesCat. No.: HY-150683CAS No.: 3031654-46-0NC-III-49-1 is a potent bivalent bromodomain and extraterminal domain (BET) inhibitor. NC-III-49-1 shows binding potential for BRD4-1, BRD4-2, BRD4-T, BRDT-1, BRDT-2, BRDT-T with Kd values of 0.095, 0.32, 0.29, 0.089, 5.5, 0.058 nM, respectively. NC-III-49-1 shows antiproliferative activity. NC-III-49-1 decreases the expression of c-Myc.
