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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Bioactivity Comments |
Pevonedistat (MLN4924) inhibits purified NAE activity in vitro with an IC50 of 4.7 nM, and has anti-tumour activity in human HCT-116 tumour cell xenografts [1]. |