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
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Zhong, H., Liu, L., Chan, D., Wang, H., Chan, P., Ma, D., & Leung, C. (2014). Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme. Biochimie, 102, 211-215. https://doi.org/10.1016/j.biochi.2014.03.005