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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HJB97
0 ImagesHJB97 is a high-affinity BET inhibitor with Ki values of 0.9 nM (BRD2 BD1), 0.27 nM (BRD2 BD2), 0.18 nM (BRD3 BD1), 0.21 nM (BRD3 BD2), 0.5 nM (BRD4 BD1), and 1.0 nM (BRD4 BD2). HJB97 can serve as a ligand for target protein (Ligands for Target Protein for PROTAC) for the development of PROTAC BET degraders with antitumor activity. HJB97 can be used for the synthesis of BETd-260 (HY-101519).
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KB02-JQ1
0 ImagesKB02-JQ1 is a highly selective and PROTAC-based BRD4 degrader (molecular glue), but does not degrade BRD2 or BRD3. KB02-JQ1 promotes BRD4 degradation by covalently modifying DCAF16 (E3 ligase) and can improve the durability of protein degradation in biological systems. JQ1 binds ubiquitin E3 ligase ligand KB02 via a linker to form KB02-JQ1.
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BRD4 degrader-3
0 ImagesBRD4 degrader-3 is a molecular glue degrader targeting BRD4, with binding activity towards the BD1 and BD2 domains of BRD4. BRD4 degrader-3 regulates the activity of BRD4. BRD4 degrader-3 inhibits MYC expression in cancer cells. BRD4 degrader-3 suppresses cell proliferation. BRD4 degrader-3 can be used in research related to acute myeloid leukemia and prostate cancer.
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MZP-54
0 ImagesMZP-54 is a PROTAC degrader that selectively targets BRD3/BRD4, with a DC50 of < 0.05 μM in AML cells. MZP-54 recruits VHL to form a ternary complex, induces BRD3/BRD4 degradation via the ubiquitin-proteasome pathway, inhibits c-Myc expression, and exerts antiproliferative activity. MZP-54 can be used for the research of acute myeloid leukemia.
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RVX-297
0 ImagesCat. No.: HY-114504CAS No.: 1044871-04-6RVX-297 is a potent, orally active BET bromodomain inhibitor with selectivity for BD2. RVX-297 shows IC50s of 0.08, 0.05, and 0.02 μM for BRD2(BD2), BRD3(BD2), and BRD4(BD2), respectively. RVX-297 suppresses inflammatory gene expression in multiple immune cell types. RVX-297 is effective in acute inflammation and autoimmunity models.
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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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BD-9136
0 ImagesBD-9136 is a selective BRD4 PROTAC degrader with a DC50 of 1.2 nM, and exhibits a selectivity of ≥1000-fold over BRD2 and BRD3. BD-9136 preferentially forms a ternary complex with the BD1 domain of BRD4, and downregulates the expression of B7-H4 by disrupting the PR-P300-BRD4 axis. BD-9136 depletes BRD4 protein in tumor tissues, inhibits tumor growth, reduces B7-H4 protein expression, increases CD8+ T cell infiltration, and enhances tumor sensitivity to anti-PD-L1. Degradation of BRD4 by BD-9136 rescues the erythroid differentiation block induced by LSD1 inhibition, and transient administration restores erythroid output while retaining HbF induction. BD-9136 causes no adverse effects in mice at effective doses. BD-9136 can be used in studies related to acute myeloid leukemia, acute lymphoblastic leukemia and breast cancer.
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BET-IN-31
0 ImagesBET-IN-31 is a potent BET inhibitor and a ligand for target BRD4 protein for PROTACT GNE-987 (HY-129937A).
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JQ1-TCO
0 ImagesCat. No.: HY-148864Purity: 99.95%JQ1-TCO is the double bond E configuration of JQ1-TCO (HY-148864A). JQ1-TCO is a derivative of JQ1 (HY-13030), an inhibitor of BET. JQ1-TCO is suitable for click chemistry and can be used as molecular probes in vitro and in vivo.
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SRX3177
0 ImagesSRX3177 is a triple inhibitor of CDK4/6, PI3K, and BRD4, with IC50s of <2.5 nM (CDK4), 3.3 nM (CDK6), 33 nM (BRD4 BD1), 89 nM (BRD4 BD2), 79 nM (PI3Kα), 83 nM (PI3Kδ), 3.18 μM (PI3Kγ) , respectively. SRX3177 blocks the interaction between the SARS-CoV-2 E protein and the BRD2/4 BD1 domain, restores E protein-attenuated NF-κB activity. SRX3177 exerts broad cytotoxic activity against cancer cells. SRX3177 can be used for the study of anti-SARS-CoV-2 and cancer.
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TD-428
0 ImagesTD-428 is a BRD4/BET PROTAC degrader. TD-428 induces the degradation of BRD4 and BET proteins via the ubiquitin-proteasome pathway by recruiting cereblon, thereby inhibiting C-MYC transcription and cancer cell proliferation. TD-428 can be used in the research of metastatic castration-resistant prostate cancer and prostate cancer.
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SJ995973
0 ImagesSJ995973 is a BRD4 PROTAC degrader with DC50 values of 0.87 nM (12 h) and 0.16 nM (24 h), respectively. SJ995973 induces the formation of a ternary complex between purified BRD4 and CRBN-DDB1 proteins, with an IC50 of 17 nM against CRBN. SJ995973 inhibits the viability of human acute myeloid leukemia cells. SJ995973 can be used in studies related to acute myeloid leukemia and medulloblastoma.
