Article
Chemistry, Medicinal
Yuantao Fu, Yanzhi Zhang, Haiying Sun
Summary: Dysfunction of BET family proteins is associated with various human diseases, making them promising targets for drug development. Most current clinical BET inhibitors lack selectivity, but selective inhibitors targeting BD1 and BD2 are being developed to elucidate their distinct functions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Mandika Chetry, Adheesh Bhandari, Yue Lin
Summary: This study indicates that high expression of BET family genes, including BRD2, BRD3, and BRDT, is associated with a better prognosis in ovarian cancer patients. These genes could serve as predictive prognostic indicators for ovarian carcinoma.
Review
Chemistry, Medicinal
Ewelina Kulikowski, Brooke D. Rakai, Norman C. W. Wong
Summary: The clinical development of BET protein inhibitors is unique, as they are being widely evaluated for treating various human diseases due to their novel mechanism of action. Among the BET protein family, BRD4 is extensively studied, and its activity at latent enhancers is a representative example of BET protein function. The role of BET proteins in embryonic development, cancer, cardiovascular, autoimmune, and metabolic diseases makes them attractive targets for therapeutic intervention.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Chemistry, Medicinal
Xuetao Chen, Fanying Meng, Jingtian Zhang, Zijian Zhang, Xuan Ye, Weikun Zhang, Yuanyuan Tong, Xinrui Ji, Rujun Xu, Xiao-Li Xu, Qi-Dong You, Zheng-Yu Jiang
Summary: Sepsis is a global health problem and BRD4 inhibitor 27 could be a potential candidate for sepsis treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Dayu Wu, Qiong Duan
Summary: BET proteins play a key role in transcriptional regulation, particularly in metabolic processes such as adipogenesis and metaflammation. Recent studies have shown their involvement in diseases such as cancer and inflammation. This article discusses the latest research on BET proteins and their regulation of metabolism in cellular and animal models, and summarizes data from randomized clinical trials evaluating BET inhibitors for the treatment of metabolic diseases.
Review
Chemistry, Medicinal
Lu Feng, Guan Wang, Yi Chen, Gu He, Bo Liu, Jie Liu, Cheng-Ming Chiang, Liang Ouyang
Summary: BRD4, a chromatin reader protein in the BET family, regulates cellular processes by binding acetylated histones and non-histone proteins. Designing dual-target inhibitors of BET bromodomains is a rational strategy in cancer treatment.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Noah R. Flynn, Michael D. Ward, Mary A. Schleiff, Corentine M. C. Laurin, Rohit Farmer, Stuart J. Conway, Gunnar Boysen, S. Joshua Swamidass, Grover P. Miller
Summary: The 3,5-dimethylisoxazole motif is widely used in BET inhibitors but may lead to the formation of toxic reactive metabolites. A study combining deep neural models and experimental validation predicted the bioactivation pathways of these inhibitors, with a focus on novel extended quinone-methides. The results highlighted the need to improve overall bioactivation scaling and potential concerns for toxicity in the development of new drug leads.
Review
Oncology
Hui-Yan Sun, Song-Tao Du, Ya-Yun Li, Guang-Tong Deng, Fu-Rong Zeng
Summary: This review discusses the role of BET proteins in gastrointestinal cancers and highlights the therapeutic potential of targeting BET proteins for the treatment of these cancers.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2022)
Article
Oncology
Yuting Meng, Xixi Qian, Li Zhao, Nan Li, Shengjie Wu, Baoan Chen, Tong Sun, Xuerong Wang
Summary: The study found that BETs were upregulated in osimertinib resistant H1975 cells, and TSA could decrease BET expression and enhance the growth inhibitory effect of JQ1, providing new strategies for the treatment of osimertinib resistance.
CANCER CELL INTERNATIONAL
(2021)
Review
Oncology
Jiacheng Lai, Ziqiang Liu, Yulei Zhao, Chengyuan Ma, Haiyan Huang
Summary: I-BET151, an inhibitor of BET proteins, demonstrates potential in cancer treatment by affecting cell cycle, signaling pathways, tumor microenvironment, and telomere elongation. Combination with other drugs can alleviate drug resistance, and even induce cell reprogramming without passing through pluripotent state. Research on I-BET151's anticancer mechanism may lead to new clinical strategies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Developmental Biology
Tyler J. Butsch, Olga Dubuisson, Alyssa E. Johnson, K. Adam Bohnert
Summary: Valosin-containing protein (VCP) plays an important role in regulating protein homeostasis by binding and extracting ubiquitylated cargo. It is not well understood how VCP functions in germline development, especially in males. Using the Drosophila male germline as a model system, researchers found that VCP translocates from the cytosol to the nucleus during germ cell differentiation and promotes spermatocyte gene expression by downregulating a repressive histone modification.
Article
Biochemistry & Molecular Biology
Siao Chen, Yi He, Yajiao Geng, Zhi Wang, Lu Han, Weiwei Han
Summary: The BET subfamily, the most studied subfamily of bromodomain-containing proteins, plays a role in regulating acetylation signal transduction and has diverse physiological functions. Through molecular dynamics simulations and computational analysis, this study found that Cpd19 had the best binding effect with BRD4 and identified a crucial role of Phe83 in the binding of Cpd9 and Cpd19 to BRD4. These findings provide valuable insights for further research on the BCPs family.
Review
Pharmacology & Pharmacy
Yanli Sun, Jie Han, Zhanzhao Wang, Xuening Li, Yanhua Sun, Zhenbo Hu
Summary: The upregulated expression of BET proteins is closely related to hematological malignancies and solid tumors. Ten BET inhibitors currently in clinical trials showed exposure-dependent thrombocytopenia, and further efforts are needed to explore optimal dosing schemes for maximizing their efficacy.META_DESCRIPTION
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Katherine L. Jones, Dominic M. Beaumont, Sharon G. Bernard, Rino A. Bit, Simon P. Campbell, Chun-wa Chung, Leanne Cutler, Emmanuel H. Demont, Kate Dennis, Laurie Gordon, James R. Gray, Michael Haase, Antonia J. Lewis, Scott McCleary, Darren J. Mitchell, Susanne M. Moore, Nigel Parr, Olivia J. Robb, Nicholas Smithers, Peter E. Soden, Colin J. Suckling, Simon Taylor, Ann L. Walker, Robert J. Watson, Rab K. Prinjha
Summary: This study details the optimization process of the in vivo tool molecule I-BET151 towards I-BET282E, a molecule with properties suitable for clinical progression, in order to reduce the risk of compound attrition due to related toxicity findings.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Alessandra Cipriano, Ciro Milite, Alessandra Feoli, Monica Viviano, Giacomo Pepe, Pietro Campiglia, Giuliana Sarno, Sarah Picaud, Satomi Imaide, Nikolai Makukhin, Panagis Filippakopoulos, Alessio Ciulli, Sabrina Castellano, Gianluca Sbardella
Summary: In this study, a series of benzimidazole-6-sulfonamide compounds were designed and synthesized, which selectively target the first bromodomain (BD1) of BET family proteins. The most promising compound showed good binding potency, improved metabolic stability, and selectivity towards BD1.