@article{d623d74a912045ba856ec14a2854aed2,
title = "Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds",
abstract = "Inactivation of the p53 transcription factor by mutation or other mechanisms is a frequent event in tumorigenesis. One of the major endogenous negative regulators of p53 in humans is hDM2, a ubiquitin E3 ligase that binds to p53 causing proteasomal p53 degradation. In this work, a library of organometallic iridium(III) compounds were synthesized and evaluated for their ability to disrupt the p53/hDM2 protein-protein interaction. The novel cyclometallated iridium(III) compound 1 [Ir(eppy)2(dcphen)](PF6) (where eppy = 2-(4-ethylphenyl)pyridine and dcphen = 4, 7- dichloro-1, 10-phenanthroline) blocked the interaction of p53/hDM2 in human amelanotic melanoma cells. Finally, 1 exhibited anti-proliferative activity and induced apoptosis in cancer cell lines consistent with inhibition of the p53/hDM2 interaction. Compound 1 represents the first reported organometallic p53/hDM2 protein-protein interaction inhibitor.",
keywords = "HDM2, Metal-based inhibitor, P53, Protein-protein interaction",
author = "Liu, \{Li Juan\} and Bingyong He and Miles, \{Jennifer A.\} and Wanhe Wang and Zhifeng Mao and Che, \{Weng Ian\} and Lu, \{Jin Jian\} and Chen, \{Xiu Ping\} and Wilson, \{Andrew J.\} and MA, \{Edmond Dik Lung\} and Leung, \{Chung Hang\}",
note = "Funding Information: This work is supported by Hong Kong Baptist University (FRG2/14-15/004), the Health and Medical Research Fund (HMRF/13121482 and HMRF/14130522), the Research Grants Council (HKBU/201913), National Natural Science Foundation of China (21575121), Guangdong Province Natural Science Foundation (2015A030313816), Hong Kong Baptist University Century Club Sponsorship Scheme 2015, the European Research Council [ERC-StG-240324] and [ERC-PoC 632207], the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12; Oligoswitch ANR-12-IS07-0001), Interdisciplinary Research Matching Scheme (RC-IRMS/14-15/06), the Science and Technology Development Fund, Macao SAR (103/2012/A3), the University of Macau (MYRG2015-00137-ICMS-QRCM, MRG023/LCH/2013/ICMS and MRG044/LCH/2015/ICMS).",
year = "2016",
month = mar,
day = "22",
doi = "10.18632/oncotarget.7369",
language = "English",
volume = "7",
pages = "13965--13975",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "12",
}
