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Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds
Liu L.-J.1; He B.2; Miles J.A.3,4; Wang W.2; Mao Z.2; Che W.I.1; Lu J.-J.1; Chen X.-P.1; Wilson A.J.3,4; Ma D.-L.2; Leung C.-H.1
2016
Source PublicationOncotarget
ISSN19492553
Volume7Issue:12Pages:13965
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.

KeywordHdm2 Metal-based Inhibitor P53 Protein-protein Interaction
DOI10.18632/oncotarget.7369
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000375687200052
The Source to ArticleScopus
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorMa D.-L.; Leung C.-H.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
3.School of Chemistry, University of Leeds, Leeds, UK
4.Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Liu L.-J.,He B.,Miles J.A.,et al. Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds[J]. Oncotarget,2016,7(12):13965.
APA Liu L.-J..,He B..,Miles J.A..,Wang W..,Mao Z..,...&Leung C.-H..(2016).Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds.Oncotarget,7(12),13965.
MLA Liu L.-J.,et al."Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds".Oncotarget 7.12(2016):13965.
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