@article{a5a20a760f834628b8af4438c548a14a,
title = "Structure-based identification of a NEDD8-activating enzyme inhibitor via drug repurposing",
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.",
keywords = "Drug repurposing, Mitoxantrone, NEDD8, Ubiquitin",
author = "Wu, {Ke Jia} and Zhong, {Hai Jing} and Guodong Li and Chenfu Liu and Wang, {Hui Min David} and Ma, {Dik Lung} and Leung, {Chung Hang}",
note = "Funding Information: This work is supported by Hong Kong Baptist University ( FRG2/16-17/007 ), the Health and Medical Research Fund ( HMRF/14130522 , 14150561 ), the Research Grants Council ( HKBU/12301115 ), the National Natural Science Foundation of China ( 21575121 ), the Guangdong Province Natural Science Foundation ( 2015A030313816 ), the Hong Kong Baptist University Century Club Sponsorship Scheme 2017 , the Interdisciplinary Research Matching Scheme ( RC-IRMS/15-16/03 ), Innovation and Technology Fund ( ITS/260/16FX) , Collaborative Research Fund ( C5026-16G ), Matching Proof of Concept Fund ( MPCF-001-2017/18 ), the Science and Technology Development Fund, Macao SAR ( 098/2014/A2 ), the University of Macau ( MYRG2015-00137-ICMS-QRCM , MYRG2016-00151-ICMS-QRCM ), and National Natural Science Foundation of China ( 21628502 ). ",
year = "2018",
month = jan,
day = "1",
doi = "10.1016/j.ejmech.2017.11.101",
language = "English",
volume = "143",
pages = "1021--1027",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
}