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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FD1-C10-CB
0 ImagesCat. No.: HY-187396FD1-C10-CB is a PROTAC degrader targeting the BRD4 protein. FD1-C10-CB binds to FEM1B to form a ternary complex with BRD4, achieving FEM1B-dependent degradation of BRD4 via the ubiquitin-proteasome system. FD1-C10-CB binds to CD36 to mediate endocytic cellular delivery, thereby enhancing its degrading activity. FD1-C10-CB mediates protein degradation through the Cullin-dependent ubiquitin-proteasome pathway, rather than the lysosomal autophagy pathway. FD1-C10-CB induces a decrease in BRD4 protein levels, and its degrading activity is competitively inhibited by FL47 or JQ1. FD1-C10-CB can be used in the research of breast cancer and osteosarcoma.
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HL435
0 ImagesCat. No.: HY-161769HL435 is a BRD4 PROTAC degrader with DC50 values of 11.9 nM (MDA-MB-231 cells) and 21.9 nM (MCF-7 cells), respectively. HL435 recruits the CRL4DCAF11 E3 ubiquitin ligase complex to degrade BRD4 via the ubiquitin-proteasome system. HL435 induces cell cycle arrest and apoptosis (apoptosis) in cancer cells, downregulates the expression levels of cyclin D1 and cyclin B1, activates caspase-9, and induces PARP1 cleavage. HL435 exerts anti-tumor activity both in vitro and in mouse xenograft tumor models. HL435 can be used for the research of breast cancer and prostate cancer.
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PI3Kα-IN-28
0 ImagesCat. No.: HY-178984CAS No.: 3095278-75-1PI3Kα-IN-28 (Compound 23) is an efficient dual targeted PI3K/BRD4 inhibitor. PI3Kα-IN-28 can inhibit the proliferation of various cells, such as KYSE180 and KYSE450 cells. PI3Kα-IN-28 can concentration dependently inhibit migration and colony formation, induce G0/G1 phase arrest, significantly inhibit DNA synthesis, and significantly increase the proportion of senescent cells. PI3Kα-IN-28 can inhibit the expression of p-AKT and c-Myc and activate the AMPK-p27 pathway. PI3Kα-IN-28 can be used for research on cancers such as esophageal cancer.
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PROTAC BRD4 Degrader-20
0 ImagesCat. No.: HY-153820CAS No.: 2086300-61-8PROTAC BRD4 Degrader-20 (Compound 195) is a PROTAC degrader that targets BRD4 for degradation by recruiting VHL. PROTAC BRD4 Degrader-20 is applicable to the research of diffuse large B-cell lymphoma.
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BET BD2-IN-1
0 ImagesCat. No.: HY-155680CAS No.: 2677039-24-4
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BRD4-IN-11
0 ImagesCat. No.: HY-175033BRD4-IN-11 is an orally active and selective BRD4 inhibitor (IC50 = 26.35 nM (BD1), IC50 = 72.81 nM (BD2)). BRD4-IN-11 is approximately 3- to 18-fold more potent against BRD4 than againstBRD2, BRD3, and BRDT. BRD4-IN-11 enhances H2S release and inhibits the upregulation of fibrotic markers (α-SMA and fibronectin), c-Myc, and CDC25B. BRD4-IN-11 reduces apoptosis in LO2 hepatocytes. BRD4-IN-11 significantly improves liver and lung function in a hepatopulmonary fibrosis model and can be used to study hepatopulmonary fibrosis.
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YT117R
0 ImagesCat. No.: HY-169148YT117R is a PROTAC degrader targeting BRD4. YT117R binds stereoselectively and site-specifically to the cysteine residue C1113 of DCAF1 to form a covalent interaction. YT117R promotes BRD4 degradation via a DCAF1-dependent, proteasome- and cullin-RING E3 ligase-mediated process. YT117R exhibits stereoselective activity dependent on wild-type DCAF1, which is blocked by the DCAF1C1113A mutation.
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PROTAC BRD4 Degrader-18
0 ImagesCat. No.: HY-134822CAS No.: 1949837-13-1PROTAC BRD4 Degrader-18 is a PROTAC BRD4 degrader. PROTAC BRD4 Degrader-18 binds to BRD4 and recruits E3 ubiquitin ligase, inducing ubiquitination and proteasomal degradation of BRD4. PROTAC BRD4 Degrader-18 exhibits antiproliferative activity against ovarian cancer cell lines. PROTAC BRD4 Degrader-18 can be used in research related to ovarian cancer.
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BRD4-IN-10
0 ImagesCat. No.: HY-174348CAS No.: 3051852-76-4BRD4-IN-10 (Compound 31) is a selective BRD4 inhibitor with an IC50 of 13.5 nM. BRD4-IN-10 can exert anti-inflammatory and anti-fibrotic effects. BRD4-IN-10 also has good metabolic stability, pharmacokinetic properties and safety. BRD4-IN-10 can be used in the research of renal fibrosis diseases.
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PROTAC BRD4 Degrader-6
0 ImagesCat. No.: HY-131203CAS No.: 2410947-56-5PROTAC BRD4 Degrader-6 (compound 32a) is a potent small-molecule BRD4PROTAC degrader with IC50 value of 2.7 nM for BRD4 BD1. PROTAC BRD4 Degrader-6 potently degrades BRD4 protein and inhibits the expression of c-Myc. PROTAC BRD4 Degrader-6 inhibits the proliferation of pancreatic cancer cell line BxPC3 and induces apoptosis. PROTAC BRD4 Degrader-6 can be used for human pancreatic cancer research.
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PROTAC BET Degrader-17
0 ImagesCat. No.: HY-181869CAS No.: 2409674-38-8PROTAC BET Degrader-17 is a potent BET protein PROTAC degrader. By recruiting the VHL E3 ligase, PROTAC BET Degrader-17 specifically degrades BRD2, BRD3 (DC50=0.09 nM) and BRD4 (IC50=4.3 nM). PROTAC BET Degrader-17 exhibits strong anti-tumor activity in acute myeloid leukemia (AML) studies; it not only inhibits cancer cell proliferation, induces cell cycle arrest and apoptosis, but also effectively suppresses tumor growth in xenograft mouse models. PROTAC BET Degrader-17 can be used to explore targeted therapies for acute myeloid leukemia.
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KWZL-7f15
0 ImagesCat. No.: HY-182036KWZL-7f15 is a dual CDK6/BRD4 inhibitor with an IC50 of 31.81 nM against human CDK6. KWZL-7f15 inhibits the CDK6-RB axis and BRD4-Myc axis, and also acts as a pan-BET inhibitor. KWZL-7f15 exhibits antiproliferative activity against triple-negative breast cancer cells. KWZL-7f15 shows antitumor activity in xenograft mouse models. KWZL-7f15 can be used in studies related to triple-negative breast cancer.
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PROTAC BRD4 Degrader-16
0 ImagesCat. No.: HY-143327CAS No.: 2585561-36-8PROTAC BRD4 Degrader-16 is a BRD4 PROTAC degrader. PROTAC BRD4 Degrader-16 induces sustained degradation of both long and short isoforms of BRD4 in cancer cells, causes cell cycle arrest, and exhibits only extremely low apoptosis effects. PROTAC BRD4 Degrader-16 can be used in studies related to acute myeloid leukemia.
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QS-57
0 ImagesCat. No.: HY-169081QS-57 is a heterobifunctional targeted protein localization (TPL) agent. QS-57 binds to BRD4 via its JQ1 domain and covalently targets 14-3-3σ to form a ternary complex. QS-57 sequesters nuclear BRD4 in the cytoplasm, impairing the nuclear transcriptional regulatory function mediated by BRD4. QS-57 significantly reduces the nuclear BRD4 protein level and increases the cytoplasmic BRD4 protein abundance in cancer cells. QS-57 can be used for research on breast cancer and colorectal cancer.
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PROTAC BRD4 Degrader-23
0 ImagesCat. No.: HY-161093PROTAC BRD4 Degrader-23 is a visible light-regulated BRD4 PROTAC degrader, with DC50 values of 6871 nM and < 30 nM in the dark and under light exposure, respectively; its IC50 values are 1172 nM and 140 nM under the corresponding conditions. PROTAC BRD4 Degrader-23 shows inhibited activity in dark environments, and recovers BRD4 degradation ability upon irradiation with 405 nm visible light. PROTAC BRD4 Degrader-23 inhibits tumor cell proliferation in a visible light-dependent manner. PROTAC BRD4 Degrader-23 can be used in studies of BRD4-dependent B-cell lymphoma.
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PROTAC BRD4 Degrader-28
0 ImagesCat. No.: HY-170808PROTAC BRD4 Degrader-28 is a PROTAC degrader targeting BRD4, with a DC50 of 5.4 nM for BRD4 in HEK293 cells. PROTAC BRD4 Degrader-28 binds to the CRBN E3 ubiquitin ligase, forms a ternary complex with BRD4, and thereby mediates the ubiquitination and proteasomal degradation of BRD4. PROTAC BRD4 Degrader-28 can be used in cancer research.
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PROTAC BRD4 Degrader-27
0 ImagesCat. No.: HY-162875CAS No.: 2407163-44-2PROTAC BRD4 Degrader-27 is a selective cereblon-mediated BRD4 PROTAC degrader. PROTAC BRD4 Degrader-27 exhibits anticancer activity, induces G1 phase arrest, and inhibits DNA synthesis and colony formation. PROTAC BRD4 Degrader-27 suppresses HCC1806 tumor growth in xenograft mouse models. PROTAC BRD4 Degrader-27 can be used in breast cancer-related research.
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PARP1/BRD4-IN-2
0 ImagesCat. No.: HY-150613CAS No.: 3037993-97-5PARP1/BRD4-IN-2 is a potent and selective PARP1 and BRD4 inhibitor with IC50 values of 197 nM and 238 nM, respectively. PARP1/BRD4-IN-2 inhibits DNA damage repair, arrests G0/G1 transition and induces apoptosis. PARP1/BRD4-IN-2 has anti-tumor activity in MDA-MB-468 xenograft mouse model. PARP1/BRD4-IN-2 can be used for researching triple-negative breast cancer (TNBC).
