Department of Chemistry
Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme
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. © 2014 The Authors. Published by Elsevier Masson SAS.
Inhibitor, NEDD8-activating enzyme, Repurposing, Structure-based, Virtual screening
Source Publication Title
Zhong, Hai-Jing, Li-Juan Liu, Daniel Shiu-Hin Chan, Hui-Min Wang, Philip Wai Hong Chan, Dik-Lung Ma, and Chung-Hang Leung. "Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme." Biochimie 102 (2014): 211-215.