MLN 4924

Biological Activity

MLN 4924 (TAK 924) is a potent and selective NEDD8 activating enzyme (NAE) inhibitor (IC₅₀ = 4.7 nM). MLN 4924 exhibits selectivity over closely related enzymes UAE, UBA6, SAE, and ATG7 (IC₅₀ = 1.5, 1.8, 8.2, and >10 μM, respectively), and displays minimal activity at adenosine receptors and a panel of 12 cellular kinases. MLN 4924 exhibits cyotoxicity in several human tumor-derived cell lines and causes liver damage in SD rats, when given with TNF-α. It blocks the NEDD8 pathway causing DNA damage in mice bearing HCT-116 xenografts. Cell permeable.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

1. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly.
   Baek et al.
   Nature, 2020;578:461
2. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.
   Soucy et al.
   Nature, 2009;458:732
3. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.
   Brownell et al.
   Mol.Cell, 2010;37:102
4. Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo.
   Zhou et al.
   Proc.Natl.Acad.Sci.USA, 2016;113:E2935
5. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment.
   Hyer et al.
   Nat.Med., 2018;24:186
6. MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma.
   Tong et al.
   Sci.Rep., 2017;7:5599
7. The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-α to activate apoptosis.
   Wolenski et al.
   Cell Death Discov., 2015;1:doi: 10.1038

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