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The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.
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http://dx.doi.org/10.13345/j.cjb.220420 | DOI Listing |
J Control Release
September 2025
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China. Electronic address:
Radiotherapy (RT) is a key component of comprehensive cancer treatment regimens; nevertheless, its concomitant immunosuppression may diminish therapeutic efficacy. In this study, we developed an injectable hydrogel system for the local delivery of PROteolysis TArgeting Chimeras (PROTACs), achieved by loading tumor cell membrane-fused liposome nanoparticles to enhance the anti-tumor effect. The system targeted Bromodomain-containing protein 4 (BRD4), and combined treatment with RT promoted DNA damage, reduced DNA repair and decreased tumor cell proliferation and survival.
View Article and Find Full Text PDFJ Med Chem
September 2025
Key Laboratory of Marine Drugs and Key Laboratory of Evolution and Marine Biodiversity (Ministry of Education), School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.
BRD4, a bromodomain-containing protein, has emerged as an attractive therapeutic target for various diseases. Selective inhibition of the bromodomain is gaining traction as a promising strategy for targeted drug discovery. Based on bioisosterism-guided optimization of RVX-OH (), a pan-BET inhibitor, we designed and synthesized a series of novel quinazolin-4(3)-one derivatives as potent BRD4 inhibitors.
View Article and Find Full Text PDFPharmacol Rep
September 2025
Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, India.
Epigenetic modulation has emerged as a central strategy that can change the fate of tumour cells to offer more rational and precise approaches by modulating reversible changes in chromatin structure, regulating gene expression without altering DNA sequence. Many reports have indicated the contributions of abnormal epigenetic alterations, particularly DNA methylation and histone modification patterns, as well as their association with non-coding RNA interactions during cancer emergence, development or resistance to standard therapies. Ongoing studies on various inhibitors also demonstrate encouraging preclinical results and potent inhibitory activity.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
Smooth muscle cell (SMC) differentiation plays a crucial role in angiogenesis and vasculogenesis during embryonic development. The underlying mechanisms controlling SMC differentiation, especially progenitor-specific regulation, however, remain largely unclear. In this study, we identified bromodomain-containing protein 4 (BRD4) as a novel regulator for SMC differentiation.
View Article and Find Full Text PDFNeoplasia
October 2025
Institute of Environmental Medicine and Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University, Hangzhou 311121, China; Skin Disease Research Institute, The 2nd Hospital, Zhejiang University S
The BRAF pathway and epigenetic machinery are central to melanoma pathogenesis. However, how these processes intersect and their potential for synthetic lethality remains unclear. Here, we identified a BRAF-driven epigenetic mechanism in melanoma that involves a H3K27 methylation-to-acetylation switch, facilitating metabolic adaptation to targeted therapies.
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