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Article

Treatment-emergent mutations in NAEβ confer resistance to the NEDD8-activating enzyme inhibitor MLN4924.

Cancer cell - 20 Mar 2012

Milhollen Michael A, Thomas Michael P, Narayanan Usha, Traore Tary, Riceberg Jessica, Amidon Benjamin S, Bence Neil F, Bolen Joseph B, Brownell James, Dick Lawrence R, Loke Huay-Keng, McDonald Alice A, Ma Jingya, Manfredi Mark G, Sells Todd B, Sintchak Mike D, Yang Xiaofeng, Xu Qing, Koenig Erik M, Gavin James M, Smith Peter G

Abstract excerpt

MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct. In cell and xenograft models of cancer, we identified treatment-emergent heterozygous mutations in the adenosine triphosphate binding pocket and...

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Identifiers

PMID: 22439935
DOI: 10.1016/j.ccr.2012.02.009

Genes

NEDD8

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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