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ID: ALA4138244
Journal: Eur J Med Chem
Title: Structure-based identification of a NEDD8-activating enzyme inhibitor via drug repurposing.
Authors: Wu KJ, Zhong HJ, Li G, Liu C, Wang HD, Ma DL, Leung CH.
Abstract: NEDD8-activating enzyme (NAE) is an essential player of the NEDD8 conjugation pathway that regulates protein degradation. Meanwhile, drug repurposing is a cost-efficient strategy to identify new therapeutic uses for existing scaffolds. In this report, mitoxantrone (1) was repurposed as an inhibitor of NAE by virtual screening of an FDA-approved drug database. Compound 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity and was competitive with ATP. Furthermore, compound 1 induced apoptosis of colorectal adenocarcinoma cancer cells through inhibiting the degradation of the neddylation substrate p53.
CiteXplore: 29232579