Identification of NAE inhibitors exhibiting potent activity in leukemia cells: exploring the structural determinants of NAE specificity

…, J Berman, A Roughton, S Dhe-Paganon…

Index: Lukkarila, Julie L.; Da Silva, Sara R.; Ali, Mohsin; Shahani, Vijay M.; Xu, G. Wei; Berman, Judd; Roughton, Andrew; Dhe-Paganon, Sirano; Schimmer, Aaron D.; Gunning, Patrick T. ACS Medicinal Chemistry Letters, 2011 , vol. 2, # 8 p. 577 - 582

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Citation Number: 14

Abstract

MLN4924 is a selective inhibitor of the NEDD8-activating enzyme (NAE) and has advanced into clinical trials for the treatment of both solid and hematological malignancies. In contrast, the structurally similar compound 1 (developed by Millennium: The Takeda Oncology Company) is a pan inhibitor of the E1 enzymes NAE, ubiquitin activating enzyme (UAE), and SUMO-activating enzyme (SAE) and is currently viewed as unsuitable for clinical use ...