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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PROTAC BRD4 Degrader-37
0 ImagesCat. No.: HY-175225PROTAC BRD4 Degrader-37 is a BRD4 PROTAC degrader with a DC50 of 36.4 nM. PROTAC BRD4 Degrader-37 recruits the E3 ubiquitin ligase TRIM21, binds to the PRYSPRY domain of TRIM21 (KD = 123 nM), and thereby mediates the ubiquitination and degradation of BRD4. PROTAC BRD4 Degrader-37 exhibits cytotoxicity against PANC-1 cells (GI50 = 0.282 μM). PROTAC BRD4 Degrader-37 can be used in studies related to pancreatic cancer.
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PROTAC BRD4 Degrader-32
0 ImagesCat. No.: HY-176449PROTAC BRD4 Degrader-32 is a CRBN-recruiting PROTAC degrader targeting BRD4 (DC50=0.2 nM in HEK293 cells). PROTAC BRD4 Degrader-32 exhibits an IC50 of 0.05 μM against human CRBN and an IC50 of 22 nM against human BRD4. PROTAC BRD4 Degrader-32 induces reduced degradation of CK1α and WIZ, causes low-level degradation of IKZF1, and does not regulate GSPT1. PROTAC BRD4 Degrader-32 holds promise for research on BRD4-related cancers (such as hematological malignancies).
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SB-284851-BT
0 ImagesCat. No.: HY-136794CAS No.: 219769-23-0SB-284851-BT is an inhibitor of BRD4/p38α/BRDT. SB-284851-BT inhibits BRD4-BD1 (IC50=1.7 µM), p38α (Kd=0.47 nM), BRDT (1) (IC50=18 µM) and BRD4 (1)(IC50=3.7 µM). SB-284851-BT reduces IL-8 production by inhibiting p38α, as well as inhibiting BRD4 to down-regulates c-Myc and NF-κB gene pathways in cancer. SB-284851-BT can combined with the bromine domain and extra terminal (BET).
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3-Methylcarbostyril
0 ImagesCat. No.: HY-W265951CAS No.: 2721-59-73-Methylcarbostyril (compound 5) is a BRD4 BD1 inhibitor with a pIC50 of 4.4.
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BET-IN-15
0 ImagesCat. No.: HY-153945CAS No.: 2408994-22-7BET-IN-15 (compound 1) is a potent and orally active BET inhibitor with IC50 values of 0.64，0.25 nM for BRD4-BD1，BRD4-BD2，respectively. BET-IN-15 shows antiproliferative activity.
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MM-02-08
0 ImagesCat. No.: HY-161167MM-02-08 is a BRD4 PROTAC degrader with a DC50 of approximately 10 nM. MM-02-08 mediates mono-ubiquitination and poly-ubiquitination modifications of target proteins without impairing cell viability. MM-02-08 is applicable to related research on triple-negative breast cancer, prostate cancer, and other diseases.
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PROTAC BRD2 BD1 Degrader-1
0 ImagesCat. No.: HY-175678PROTAC BRD2 BD1 Degrader-1 is a potent and selective BRD2 BD1 PROTAC degrader, with a DC50 of 65 nM, an EC50 of 423 nM, and a Kd of 69 nM against BRD2 BD1. PROTAC BRD2 BD1 Degrader-1 induces the formation of a ternary complex between the BET bromodomain and the VHL E3 ubiquitin ligase complex, triggering VCB-dependent degradation of the target bromodomain. PROTAC BRD2 BD1 Degrader-1 can be used in cancer research.
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PROTAC BET Degrader-16
0 ImagesCat. No.: HY-181867CAS No.: 2410947-65-6PROTAC BET Degrader-16 (Compound A10) is a BET PROTAC degrader with a DC50 of 0.31 nM against BRD4, and it preferentially targets BRD4 over other BET family members. PROTAC BET Degrader-16 degrades BRD2, BRD3 and BRD4 via the ubiquitin-proteasome system, a process that requires target binding and recruitment of the CRBN E3 ligase. PROTAC BET Degrader-16 induces cell cycle arrest and promotes apoptosis. PROTAC BET Degrader-16 exerts anti-tumor activity against acute myeloid leukemia.
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WNY0824
0 ImagesCat. No.: HY-143471CAS No.: 2412707-81-2Synonyms: PLK1/BRD4-IN-1WNY0824 (PLK1/BRD4-IN-1) is an orally active dual inhibitor of PLK1 and BET protein families, with IC50 values of 22, 402.5, 150.7, 103.9, and 311.9 nmol/L for PLK1, BRD2, BRD3, BRD4, and BRDT, respectively. WNY0824 induces cell cycle arrest and apoptosis by inhibiting AR- and MYC-mediated transcriptional processes. In addition, WNY0824 also inhibits tumor growth in Enzalutamide (HY-70002) resistant CRPC xenograft tumor models.
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CBP/p300/BRD4 ligand-1
0 ImagesCat. No.: HY-181759CAS No.: 3086024-48-5CBP/p300/BRD4 ligand-1 is a small-molecule inhibitor targeting CBP, p300, and BRD4. CBP/p300/BRD4 ligand-1 competitively binds to the functional domains of target proteins without disrupting key interactions. CBP/p300/BRD4 ligand-1 can be used for the construction of dual-target PROTAC degraders (HY-181758) in studies related to prostate cancer and other cancers.
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JV8
0 ImagesCat. No.: HY-173433CAS No.: 2841716-61-6JV8 is a BRD4 PROTAC degrader with a target Kd of 0.65 μM. JV8 preferentially induces BRD4 degradation in the cytoplasm via the ubiquitin-proteasome system. JV8 exhibits dose-dependent and time-dependent BRD4 degradation activity and is capable of inducing cell apoptosis. JV8 inhibits tumor growth in a dose-dependent manner and induces BRD4 degradation in tumor tissues in vivo. JV8 can be used in research related to various cancers such as breast cancer and pancreatic cancer.
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TMU454
0 ImagesCat. No.: HY-180909TMU454 is an ASGPR-targeting GalNAc-PROTAC BRD4 degrader conjugate. TMU454 undergoes ASGPR-mediated endocytosis and CTSB cleavage to release MZ1, which selectively degrades BRD4 in ASGPR-positive hepatocellular carcinoma cells via the VHL/UPS/proteasome pathway. TMU454 inhibits cancer cell proliferation and colony formation, and suppresses tumor growth in vivo. TMU454 can be used for research related to hepatocellular carcinoma.
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PROTAC BET Degrader-15
0 ImagesCat. No.: HY-181729PROTAC BET Degrader-15 is a BET PROTAC degrader with DC50 values of <0.10 nM, <0.01 nM, and <0.01 nM against BRD2, BRD3, and BRD4, respectively. PROTAC BET Degrader-15 induces significant G2/M phase cell cycle arrest and triggers apoptosis. PROTAC BET Degrader-15 causes marked downregulation of c-Myc, accompanied by upregulation of the cell cycle inhibitory protein p21, downregulation of CDK6, and an increase in the apoptosis marker cleaved PARP. PROTAC BET Degrader-15 is applicable to the research of hematologic malignancies and lung cancer.
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LCI40
0 ImagesCat. No.: HY-183770LCI40 is an orally active dual PI3K/BRD4 inhibitor (PI3Kα IC50 = 0.071 μM, PI3Kβ IC50 = 0.17 μM, PI3Kγ IC50 = 0.66 μM, PI3Kδ IC50 = 0.072 μM, BRD4 BD1 IC50 = 0.19 μM, and BRD4 BD2 IC50 = 1.88 μM. LCI40 inhibits phosphorylation of pAKT (S473) and suppresses c-MYC levels in mantle cell lymphoma cells. LCI40 displays immunomodulatory capacity with minimal toxicity to normal mouse immune cells. LCI40 can be used for the research of mantle cell lymphoma.
