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Disrupting Acetyl-lysine Interactions: Recent Advance in the Development of BET Inhibitors

[ Vol. 19 , Issue. 10 ]

Author(s):

Fa Zhang and Shutao Ma*   Pages 1148 - 1165 ( 18 )

Abstract:


Background: Histone acetylation is an essential approach of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by Bromodomainscontaining protein (BRDs). In recent years, many researchers have found that a variety of malignancy, inflammatory and other diseases occurrences and developments are associated with BRD4 expression disorders or dysfunction. Meanwhile, many inhibitors of the extra-terminal (BET) family have been reported in many papers.

Objective: This review summarized those newly found BET inhibitors, their mechanism of action and bioactivity. Secondly, those compounds were mainly classified based on their structures and their structure-activity relationship information was discussed. Beyond that, every compound’s design strategy was pointed out.

Results and Conclusion: Herein, the recent advances reported were reviewed for discovering more excellent small molecule inhibitors. Currently, in addition to compound 4, compounds 7, 22 and 90, have also been into the clinical trial stage. In the view of the outstanding performance of BET inhibitors in anti-tumor, anti-inflammatory and anti-drug resistance, we believe that more and more BET inhibitors will become the new epigenetic therapy for cancer, inflammation and autoimmune disease in clinical practice in the near future.

Keywords:

BET inhibitors, acetyl-lysine, transcriptional regulation, chromatin, BRDs, SARs.

Affiliation:

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012

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