Inhibition of BET bromodomains as a therapeutic strategy for cancer drug discovery

Lei-lei Fu, Mao Tian, Xiang Li, Jing-jing Li, Jian Huang, Liang Ouyang, Yonghui Zhang and Bo Liu _

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Oncotarget. 2015; 6:5501-5516. https://doi.org/10.18632/oncotarget.3551

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Lei-lei Fu1,*, Mao Tian1,*, Xiang Li1,*, Jing-jing Li1, Jian Huang2, Liang Ouyang1, Yonghui Zhang1,3 and Bo Liu1

1 State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, Department of Urology, West China Hospital, Sichuan University, Chengdu, China

2 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China

3 Collaborative Innovation Center for Biotherapy, Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China

* These authors contributed equally to this work

Correspondence to:

Bo Liu, email:

Jian Huang, email:

Keywords: bromodomain, BRD2/4, BRD3, BRDT, BET inhibitor

Received: January 22, 2015 Accepted: February 13, 2015 Published: March 12, 2015


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.

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