A metal-based inhibitor of NEDD8-activating enzyme.

A cyclometallated rhodium(III) complex [Rh(ppy)(2)(dppz)](+) (1) (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine) has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE). The complex inhibited NAE activity in cell-free and c...

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Autores principales:	Hai-Jing Zhong, Hui Yang, Daniel Shiu-Hin Chan, Chung-Hang Leung, Hui-Min Wang, Dik-Lung Ma
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/022f413bb4b34c8cb60da3d86a5c59c9
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id	oai:doaj.org-article:022f413bb4b34c8cb60da3d86a5c59c9
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spelling	oai:doaj.org-article:022f413bb4b34c8cb60da3d86a5c59c92021-11-18T08:08:17ZA metal-based inhibitor of NEDD8-activating enzyme.1932-620310.1371/journal.pone.0049574https://doaj.org/article/022f413bb4b34c8cb60da3d86a5c59c92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23185368/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A cyclometallated rhodium(III) complex [Rh(ppy)(2)(dppz)](+) (1) (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine) has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE). The complex inhibited NAE activity in cell-free and cell-based assays, and suppressed the CRL-regulated substrate degradation and NF-κB activation in human cancer cells with potency comparable to known NAE inhibitor MLN4924. Molecular modeling analysis suggested that the overall binding mode of 1 within the binding pocket of the APPBP1/UBA3 heterodimer resembled that for MLN4924. Complex 1 is the first metal complex reported to suppress the NEDDylation pathway via inhibition of the NEDD8-activating enzyme.Hai-Jing ZhongHui YangDaniel Shiu-Hin ChanChung-Hang LeungHui-Min WangDik-Lung MaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49574 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hai-Jing Zhong Hui Yang Daniel Shiu-Hin Chan Chung-Hang Leung Hui-Min Wang Dik-Lung Ma A metal-based inhibitor of NEDD8-activating enzyme.
description	A cyclometallated rhodium(III) complex [Rh(ppy)(2)(dppz)](+) (1) (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine) has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE). The complex inhibited NAE activity in cell-free and cell-based assays, and suppressed the CRL-regulated substrate degradation and NF-κB activation in human cancer cells with potency comparable to known NAE inhibitor MLN4924. Molecular modeling analysis suggested that the overall binding mode of 1 within the binding pocket of the APPBP1/UBA3 heterodimer resembled that for MLN4924. Complex 1 is the first metal complex reported to suppress the NEDDylation pathway via inhibition of the NEDD8-activating enzyme.
format	article
author	Hai-Jing Zhong Hui Yang Daniel Shiu-Hin Chan Chung-Hang Leung Hui-Min Wang Dik-Lung Ma
author_facet	Hai-Jing Zhong Hui Yang Daniel Shiu-Hin Chan Chung-Hang Leung Hui-Min Wang Dik-Lung Ma
author_sort	Hai-Jing Zhong
title	A metal-based inhibitor of NEDD8-activating enzyme.
title_short	A metal-based inhibitor of NEDD8-activating enzyme.
title_full	A metal-based inhibitor of NEDD8-activating enzyme.
title_fullStr	A metal-based inhibitor of NEDD8-activating enzyme.
title_full_unstemmed	A metal-based inhibitor of NEDD8-activating enzyme.
title_sort	metal-based inhibitor of nedd8-activating enzyme.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/022f413bb4b34c8cb60da3d86a5c59c9
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_version_	1718422147382116352

A metal-based inhibitor of NEDD8-activating enzyme.

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