Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium (III) compounds

Status	已發表Published
	Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium (III) compounds
	Liu, L. J. ; He, B. ; Miles, J. A.; Wang, W. H. D; Mao, Z. ; Che, W. I. ; Lu, J.; Chen, X. P.; Wilson, A. J. ; Ma, D. L. ; Leung, C. H.
	2016-02-13
Source Publication	Oncotarget
ISSN	1949-2553
Pages	13965-13975
Abstract	nactivation 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 organometalliciridium(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 ofp53/hDM2 in human amelanotic melanoma cells. Finally, 1 exhibited anti-proliferative activity and induced apoptosis in cancer cell lines consistent withinhibition of the p53/hDM2 interaction. Compound 1 represents the first reported organometallic p53/hDM2 protein-protein interaction inhibitor.
Keyword	hDM2 metal-based inhibitor p53 protein-protein interaction
Language	英語English
The Source to Article	PB_Publication
PUB ID	22302
Document Type	Journal article
Collection	University of Macau
Corresponding Author	Ma, D. L. ; Leung, C. H.
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, 13965-13975.
APA	Liu, L. J. ., He, B. ., Miles, J. A.., Wang, W. H. D., Mao, Z. ., Che, W. I. ., Lu, J.., Chen, X. P.., Wilson, A. J. ., Ma, D. L. ., & Leung, C. H. (2016). Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium (III) compounds. Oncotarget, 13965-13975.
MLA	Liu, L. J. ,et al."Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium (III) compounds".Oncotarget (2016):13965-13975.

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