机构：[1]State Key Laboratory of Biotherapy and Cancer Center, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院[2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院[3]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.[4]Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院
Blocking the interactions between bromodomain and extraterminal (BET) proteins and acetylated lysines of histones by small molecules has important implications for the treatment of cancers and other diseases. Many pan-BET inhibitors have shown satisfactory results in clinical trials, but their potential for poor tolerability and toxicity persist. However, recently reported studies illustrate that some BET bromodomain (BET-BD1 or BET-BD2)-selective inhibitors have advantage over pan-inhibitors, including reduced toxicity concerns. Furthermore, some selective BET inhibitors have similar or even better therapeutic efficacy in inflammatory diseases or cancers. Therefore, the development of selective BET inhibitors has become a hot spot for medicinal chemists. Here, we summarize the known selective BET-BD1 and BET-BD2 inhibitors and review the methods for enhancing the selectivity and potency of these inhibitors based on their different modes of interactions with BET-BD1 or BET-BD2. Finally, we discuss prospective strategies that selectively target the bromodomains of BET proteins.
基金：
the National Natural Science
Foundation of China, grant numbers: 81922064, 81874290,
82073318, and 81903502, China Postdoctoral Science
Foundation, grant number: 2020M673268, Sichuan Science
and Technology Program (2019YFS0003), and National
Major Scientific and Technological Special Project for
Significant New Drugs Development (2018ZX09201018-021).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|1 区医学
小类|1 区药物化学
最新[2023]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]State Key Laboratory of Biotherapy and Cancer Center, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Chen Juncheng,Tang Pan,Wang Yuxi,et al.Targeting Bromodomain-Selective Inhibitors of BET Proteins in Drug Discovery and Development.[J].Journal of medicinal chemistry.2022,65(7):5184-5211.doi:10.1021/acs.jmedchem.1c01835.
APA：
Chen Juncheng,Tang Pan,Wang Yuxi,Wang Jiaxing,Yang Chengcan...&Ouyang Liang.(2022).Targeting Bromodomain-Selective Inhibitors of BET Proteins in Drug Discovery and Development..Journal of medicinal chemistry,65,(7)
MLA：
Chen Juncheng,et al."Targeting Bromodomain-Selective Inhibitors of BET Proteins in Drug Discovery and Development.".Journal of medicinal chemistry 65..7(2022):5184-5211
医学