Synonyms: MLN 4924 | MLN-4924 | MLN4924 | TAK-924 | TAK924
Compound class:
Synthetic organic
Comment: Pevonedistat (MLN4924) is an inhibitor of the NEDD8 activating enzyme (NAE) [1], which is a heterodimer of NAE1 (NAE1; Q13564) and UBA3 subunits. Pevonedistat is structurally similar to the NAE reaction product adenosine 5′-monophosphate (AMP), and interacts with nucleotide-binding site of NAE. NAE is essential for the NEDD8 conjugation pathway which controls the activity of the cullin-RING ubiquitin E3 ligases. NAE inhibitors are proposed to disrupt cullin-RING ligase-mediated protein turnover and to promote apoptosis in human tumour cells.
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References |
1. Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S et al.. (2009)
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature, 458 (7239): 732-6. [PMID:19360080] |
2. Zhou X, Vaishampayan U, Mahalingam D, Harvey RD, Chung KY, Sedarati F, Dong C, Faller DV, Venkatakrishnan K, Gupta N. (2022)
Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors. Invest New Drugs, 40 (5): 1042-1050. [PMID:35932388] |