Liu, L-J, He, B, Miles, JA orcid.org/0000-0001-8839-9201 et al. (8 more authors) (2016) Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds. Oncotarget, 7 (12). pp. 13965-13975. ISSN 1949-2553
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Author(s) 2016. This is an open access article, licensed under a Creative Commons Attribution 3.0 License (http://creativecommons.org/licenses/by/3.0/). |
Keywords: | metal-based inhibitor, protein-protein interaction, p53, hDM2 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Mar 2016 16:33 |
Last Modified: | 17 Feb 2022 17:10 |
Published Version: | http://dx.doi.org/10.18632/oncotarget.7369 |
Status: | Published |
Publisher: | Impact Journals |
Identification Number: | 10.18632/oncotarget.7369 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:96121 |