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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L134
0 ImagesL134 is a BRD4 PROTAC degrader with a DC50 of 7.36 nM. L134 induces BRD4 protein degradation without inhibiting BRD4 gene expression, and recruits the E3 ubiquitin ligase DCAF11 to mediate this process, which can be blocked by proteasome inhibitors (MG132 (HY-13259), PS341 (HY-10227)) and E1 ubiquitin ligase inhibitors (PYR41 (HY-13296), MLN4924 (HY-70062)). L134 inhibits cancer cell migration, promotes cancer cell apoptosis and exerts antiproliferative activity. L134 can be used in studies related to triple-negative breast cancer.
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BRD4 Inhibitor-18
0 ImagesCat. No.: HY-146660CAS No.: 2451219-73-9BRD4 Inhibitor-18 is a highly potent BRD4 inhibitor with an IC50 value of 110 nM. BRD4 Inhibitor-18 has a hydrophobic acetylcyclopentanyl side chain. BRD4 Inhibitor-18 can significantly suppress the proliferation of MV-4-11 cells with high BRD4 level. BRD4 Inhibitor-18 has apoptosis-promoting and G0/G1 cycle-arresting activity.
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BET-IN-2
0 ImagesCat. No.: HY-102044CAS No.: 2104688-91-5BET-IN-2 is a BET inhibitor with an IC50 of 52 nM for BRD4-BD1.
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JQ1-S(GlcNAc)Cq
0 ImagesCat. No.: HY-178510JQ1-S (GlcNAc) Cq is a sugar-modified BRD4 PROTAC degrader with a DC50 of 2.1 μM. JQ1-S (GlcNAc) Cq inhibits the formation of the ternary complex between CRBN and BRD4 (BD1/BD2). JQ1-S (GlcNAc) Cq serves as a substrate for O-GlcNAcase, which cleaves its O-GlcNAc domain to restore binding ability with CRBN, thereby forming a BRD4-containing ternary complex and triggering ubiquitination and proteasomal degradation of BRD4. JQ1-S (GlcNAc) Cq is applicable for cancer research.
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BRD4-BD1-IN-4
0 ImagesCat. No.: HY-187207BRD4-BD1-IN-4 is a selective BRD4 BD1 inhibitor with an IC50 of 0.82 μM and a Kd of 0.98 μM. BRD4-BD1-IN-4 downregulates the expression of c-myc and anti-apoptotic proteins, elevates ROS levels, reduces mitochondrial membrane potential, induces DNA damage and triggers apoptosis. BRD4-BD1-IN-4 inhibits the migration and proliferation of cancer cells. BRD4-BD1-IN-4 can be used in the research of lung cancer, breast cancer and colon cancer.
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PROTAC BRD4 Degrader-36
0 ImagesCat. No.: HY-175224PROTAC BRD4 Degrader-36 is a BRD4 PROTAC degrader with a DC50 of 0.649 nM. It has a Kd of 123 nM for TRIM21. PROTAC BRD4 Degrader-36 recruits the E3 ubiquitin ligase TRIM21 (Kd = 123 nM) to BRD4, leading to ubiquitination and subsequent degradation of BRD4. PROTAC BRD4 Degrader-36 exhibits cytotoxicity against PANC-1 cells (GI50 = 0.103 μM). It can be used in research related to pancreatic cancer.
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CZL-149
0 ImagesCat. No.: HY-183992CAS No.: 3094772-96-7CZL-149 is an orally active dual BET and p300/CBP bromodomains inhibitor with IC50s of 13 nM and 10.5 nM for BED4 BD1 and p300, respectively. CZL-149 reduces c-Myc and H3K27Ac levels. CZL-149 has good drug-like properties and metabolic characteristics, as well as good safety. CZL-149 can be used for the study of multiple myeloma.
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PROTAC FLT3/JAK2/BRD4 Degrader-1
0 ImagesCat. No.: HY-175610CAS No.: 3067695-20-6PROTAC FLT3/JAK2/BRD4 Degrader-1 is a FLT3/JAK2/BRD4 PROTAC degrader with DC50 values of 5.23, 0.68, and 1.17 nM, respectively. PROTAC FLT3/JAK2/BRD4 Degrader-1 induces cereblon- and proteasome-dependent degradation of FLT3, JAK2, and BRD4 via the ubiquitin-proteasome system. PROTAC FLT3/JAK2/BRD4 Degrader-1 is used in studies related to FLT3 inhibitor-resistant leukemia and acute myeloid leukemia.
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BRD4-BD1-IN-1
0 ImagesCat. No.: HY-143299CAS No.: 2761321-18-8BRD4-BD1-IN-1 (Compound 9a) is a BRD4-BD1 inhibitor with an IC50 of 38.20 μM.
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PROTAC BRD4 Degrader-26
0 ImagesCat. No.: HY-161650CAS No.: 3050769-37-1PROTAC BRD4 Degrader-26 is a light-regulated BRD4 PROTAC degrader. PROTAC BRD4 Degrader-26 induces targeted degradation of BRD4 via the ubiquitin-proteasome system. PROTAC BRD4 Degrader-26 is a degrader that can be inactivated in response to ultraviolet light. PROTAC BRD4 Degrader-26 can be used in breast cancer-related research.
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phoBET1
0 ImagesCat. No.: HY-149328CAS No.: 3033545-34-2phoBET1 is a photolabile PROTAC molecule that, upon photoactivation, functions as a BRD4 PROTAC degrader to trigger BRD4 degradation via the ubiquitin-proteasome system. Activated phoBET1 induces cancer cell apoptosis and inhibits tumor growth in xenograft mouse models. In its inactive caged state, phoBET1 exhibits only extremely low antiproliferative activity against cancer cells. phoBET1 can be applied in studies related to acute myeloid leukemia.
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PROTAC BRD4 Degrader-17
0 ImagesCat. No.: HY-143328CAS No.: 2585561-49-3PROTAC BRD4 Degrader-17 (compound 13i) is a potent PROTAC BRD4 Degrader, with IC50 values of 29.54 nM (BRD4 (BD1)) and 3.82 nM (BRD4 (BD2)). PROTAC BRD4 Degrader-17 significantly attenuates G2/M progression associated Cyclin B1 expression. PROTAC BRD4 Degrader-17 significantly induces apoptosis in MV-4-11 cells.
