Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/43431
Title: An iridium(III)-based irreversible protein-protein interaction inhibitor of BRD4 as a potent anticancer agent
Authors: Zhong, HJ
Lu, L
Leung, KH
Wong, CCL
Peng, C
Yan, SC
Ma, DL
Cai, Z
David, WHM
Leung, CH
Issue Date: 2015
Publisher: Royal Society of Chemistry
Source: Chemical science, 2015, v. 6, no. 10, p. 5400-5408 How to cite?
Journal: Chemical science 
Abstract: Bromodomain-containing protein 4 (BRD4) has recently emerged as an attractive epigenetic target for anticancer therapy. In this study, an iridium(iii) complex is reported as the first metal-based, irreversible inhibitor of BRD4. Complex 1a is able to antagonize the BRD4-acetylated histone protein-protein interaction (PPI) in vitro, and to bind BRD4 and down-regulate c-myc oncogenic expression in cellulo. Chromatin immunoprecipitation (ChIP) analysis revealed that 1a could modulate the interaction between BRD4 and chromatin in melanoma cells, particular at the MYC promoter. Finally, the complex showed potent activity against melanoma xenografts in an in vivo mouse model. To our knowledge, this is the first report of a Group 9 metal complex inhibiting the PPI of a member of the bromodomain and extraterminal domain (BET) family. We envision that complex 1a may serve as a useful scaffold for the development of more potent epigenetic agents against cancers such as melanoma.
URI: http://hdl.handle.net/10397/43431
ISSN: 2041-6520 (print)
2041-6539 (online)
DOI: 10.1039/c5sc02321a
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