@article{09725f6099ad4fbcaa88e86b97ecbcb1,
title = "An iridium(III)-based irreversible protein-protein interaction inhibitor of BRD4 as a potent anticancer agent",
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.",
author = "Zhong, {Hai Jing} and Lihua Lu and Leung, {Ka Ho} and Wong, {Catherine C.L.} and Chao Peng and Yan, {Siu Cheong} and MA, {Edmond Dik Lung} and Zongwei CAI and {David Wang}, {Hui Min} and Leung, {Chung Hang}",
note = "This work is supported by Hong Kong Baptist University (FRG2/14-15/004), Centre for Cancer and Inflammation Research, School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund (HMRF/13121482 and HMRF/14130522), the Research Grants Council (HKBU/201811, HKBU/204612, and HKBU/201913), the French National Research Agency/Research Grants Council Joint Research Scheme (AHKBU201/12 - Oligoswitch), Interdisciplinary Research Matching Scheme (RC-IRMS/14-15/06), the Science and Technology Development Fund, Macao SAR (103/2012/A3 and 098/2014/A2), the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG2015-00137-ICMS-QRCM and MRG023/LCH/2013/ICMS) and the National Science Council under the Grant nos. NSC102-2622-E-037-002, NSC102-2221-E-037-005, NSC102-2622-E-011-001-CC2 and MOST103-2221-E-037-004. We thank the project of Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, KMU-TP103G00 and KMU-TP103G02-05.",
year = "2015",
month = oct,
day = "1",
doi = "10.1039/c5sc02321a",
language = "English",
volume = "6",
pages = "5400--5408",
journal = "Chemical Science",
issn = "2041-6520",
publisher = "Royal Society of Chemistry",
number = "10",
}