http://dx.doi.org/10.1371/journal.pone.0049574">
 

Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

A metal-based inhibitor of NEDD8-activating enzyme

Language

English

Abstract

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. © 2012 Zhong et al.

Publication Date

2012

Source Publication Title

PLoS ONE

Volume

7

Issue

11

Publisher

Public Library of Science

ISSN (print)

19326203

ISSN (electronic)

19326203

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