title: Inhibition of BET bromodomains as a therapeutic strategy for cancer drug discovery.
abstract: As a conserved protein interaction module that recognizes and binds to acetylated lysine, bromodomain (BRD) contains a deep, largely hydrophobic acetyl lysine binding site. Proteins that share the feature of containing two BRDs and an extra-terminal domain belong to BET family, including BRD2, BRD3, BRD4 and BRDT. BET family proteins perform transcription regulatory function under normal conditions, while in cancer, they regulate transcription of several oncogenes, such as c-Myc and Bcl-2. Thus, targeting BET proteins may be a promising strategy, and intense interest of BET proteins has fueled the development of structure-based bromodomain inhibitors in cancer. In this review, we focus on summarizing several small-molecule BET inhibitors and their relevant anti-tumor mechanisms, which would provide a clue for exploiting new targeted BET inhibitors in the future cancer therapy.
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Lei-lei
authors: LL
authors: Fu
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Mao
authors: M
authors: Tian
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Xiang
authors: X
authors: Li
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Jing-jing
authors: JJ
authors: Li
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China.
authors: Jian
authors: J
authors: Huang
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Liang
authors: L
authors: Ouyang
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.|Collaborative Innovation Center for Biotherapy, Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China.
authors: Yonghui
authors: Y
authors: Zhang
authors: State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
authors: Bo
authors: B
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases
keywords: BET inhibitor; BRD2/4; BRD3; BRDT; bromodomain