Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme

Hai Jing Zhong; Li Juan Liu; Daniel Shiu Hin Chan; Hui Min Wang; Philip Wai Hong Chan; Dik Lung Ma; Chung Hang Leung

doi:10.1016/j.biochi.2014.03.005

Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme

Hai Jing Zhong
, Li Juan Liu
, Daniel Shiu Hin Chan
, Hui Min Wang
, Philip Wai Hong Chan
, Dik Lung Ma
, Chung Hang Leung^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

31 Citations (Scopus)

Abstract

We report the discovery of an inhibitor of NEDD8-activating enzyme (NAE) by an integrated virtual screening approach. Piperacillin 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity. Furthermore, piperacillin 1 was able to inhibit the degradation of the NAE downstream protein substrate p27^kip1. Our molecular modeling and kinetic studies suggested that this compound may act as a non-covalent ATP-competitive inhibitor of NAE.

Original language	English
Pages (from-to)	211-215
Number of pages	5
Journal	Biochimie
Volume	102
Issue number	1
DOIs	https://doi.org/10.1016/j.biochi.2014.03.005
Publication status	Published - Jul 2014

User-Defined Keywords

Inhibitor
NEDD8-activating enzyme
Repurposing
Structure-based
Virtual screening

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10.1016/j.biochi.2014.03.005

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title = "Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme",

abstract = "We report the discovery of an inhibitor of NEDD8-activating enzyme (NAE) by an integrated virtual screening approach. Piperacillin 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity. Furthermore, piperacillin 1 was able to inhibit the degradation of the NAE downstream protein substrate p27kip1. Our molecular modeling and kinetic studies suggested that this compound may act as a non-covalent ATP-competitive inhibitor of NAE.",

keywords = "Inhibitor, NEDD8-activating enzyme, Repurposing, Structure-based, Virtual screening",

author = "Zhong, \{Hai Jing\} and Liu, \{Li Juan\} and Chan, \{Daniel Shiu Hin\} and Wang, \{Hui Min\} and Chan, \{Philip Wai Hong\} and Ma, \{Dik Lung\} and Leung, \{Chung Hang\}",

note = "Funding Information: This work is supported by Hong Kong Baptist University (FRG2/12-13/021, FRG2/13-14/008), Centre for Cancer and Inflammation Research, School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund (HMRF/13121482), the Research Grants Council (HKBU/201811, HKBU/204612 and HKBU/201913), the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12), the Science and Technology Development Fund, Macao SAR (001/2012/A and 103/2012/A3) and the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG121(Y3-L2)-ICMS12-LCH and MRG023/LCH/2013/ICMS). ",

year = "2014",

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doi = "10.1016/j.biochi.2014.03.005",

language = "English",

volume = "102",

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AU - Zhong, Hai Jing

AU - Liu, Li Juan

AU - Chan, Daniel Shiu Hin

AU - Wang, Hui Min

AU - Chan, Philip Wai Hong

AU - Ma, Dik Lung

AU - Leung, Chung Hang

N1 - Funding Information: This work is supported by Hong Kong Baptist University (FRG2/12-13/021, FRG2/13-14/008), Centre for Cancer and Inflammation Research, School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund (HMRF/13121482), the Research Grants Council (HKBU/201811, HKBU/204612 and HKBU/201913), the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12), the Science and Technology Development Fund, Macao SAR (001/2012/A and 103/2012/A3) and the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG121(Y3-L2)-ICMS12-LCH and MRG023/LCH/2013/ICMS).

PY - 2014/7

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N2 - We report the discovery of an inhibitor of NEDD8-activating enzyme (NAE) by an integrated virtual screening approach. Piperacillin 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity. Furthermore, piperacillin 1 was able to inhibit the degradation of the NAE downstream protein substrate p27kip1. Our molecular modeling and kinetic studies suggested that this compound may act as a non-covalent ATP-competitive inhibitor of NAE.

AB - We report the discovery of an inhibitor of NEDD8-activating enzyme (NAE) by an integrated virtual screening approach. Piperacillin 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity. Furthermore, piperacillin 1 was able to inhibit the degradation of the NAE downstream protein substrate p27kip1. Our molecular modeling and kinetic studies suggested that this compound may act as a non-covalent ATP-competitive inhibitor of NAE.

KW - Inhibitor

KW - NEDD8-activating enzyme

KW - Repurposing

KW - Structure-based

KW - Virtual screening

UR - https://www.scopus.com/pages/publications/84901791098

U2 - 10.1016/j.biochi.2014.03.005

DO - 10.1016/j.biochi.2014.03.005

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C2 - 24657219

AN - SCOPUS:84901791098

SN - 0300-9084

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SP - 211

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JO - Biochimie

JF - Biochimie

IS - 1

ER -

Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme

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