MLN-4924
MLN4924 acts as a Nedd8-activating enzyme inhibitor, blocking proteasomal cullin protein neddylation by Cullin-RING E3 ubiquitin ligases. As a result, these proteins accumulate, inducing cell cycle arrest, senescence, autophagy, and/or apoptosis in cellular and animal models. This compound’s inhibition of neddylation decreases NF-κB-mediated release of pro-inflammatory cytokines TNF-α and IL-6. Pro-angiogenic HIF-1 also accumulates, potentially responsible for downstream inhibition of mTOR and the induction of autophagy.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18945531
| Cas No. |
905579-51-3 |
|---|---|
| Purity |
≥99% |
| Formula |
C21H25N5O4S |
| Formula Wt. |
443.16 |
| IUPAC Name |
[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate |
| Synonym |
MLN4924, Pevonedistat |
| Solubility |
Ethanol (12.5 mg/ml)DMSO (20 mg/ml)DMF (20 mg/ml) |
| Appearance |
White to off white powder |
Yan ZH, Burkhardt A, Loke HK, et al. Quantifiable analysis of cellular pathway inhibition of a Nedd8-activating enzyme inhibitor, MLN4924, using AlphaScreen. Anal Biochem. 2013 Aug 15;439(2):109-15. PMID: 23624319.
Li L, Liu B, Dong T, et al. Neddylation pathway regulates the proliferation and survival of macrophages. Biochem Biophys Res Commun. 2013 Mar 15;432(3):494-8. PMID: 23416079.
Zhao Y, Xiong X, Jia L, et al. Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis. Cell Death Dis. 2012 Sep 6;3:e386. PMID: 22951983.
Luo Z, Pan Y, Jeong LS, et al. Inactivation of the Cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells. Autophagy. 2012 Nov;8(11):1677-9. PMID: 22874562.
Nawrocki ST, Griffin P, Kelly KR, et al. MLN4924: a novel first-in-class inhibitor of NEDD8-activating enzyme for cancer therapy. Expert Opin Investig Drugs. 2012 Oct;21(10):1563-73. PMID: 22799561.
Yang D, Tan M, Wang G, et al. The p21-dependent radiosensitization of human breast cancer cells by MLN4924, an investigational inhibitor of NEDD8 activating enzyme. PLoS One. 2012;7(3):e34079. PMID: 22457814.
