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Pevonedistat HCl

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Chemical Structure| 1160295-21-5 同义名 : MLN4924 hydrochloride;Pevonedistat hydrochloride
CAS号 : 1160295-21-5
货号 : A765475
分子式 : C21H26ClN5O4S
纯度 : 98%
分子量 : 479.98
MDL号 : MFCD17215201
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(218.76 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 10 mg/mL(20.83 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that controls the activity of the cullin-RING subtype of ubiquitin ligases, thereby regulating the turnover of a subset of proteins upstream of the proteasome[3]. MLN4924 HCl (Pevonedistat hydrochloride) is an effective inhibitor of NAE (half-maximal inhibitory concentration (IC50=0.004 μM), and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC50=1.5, 8.2, 1.8 and >10 μM, respectively)[4]. Pevonedistat (MLN4924) rapidly inhibits cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner in gastric cancer cells, and significantly suppresses migration by transcriptionally activating E-cadherin and repressing MMP-9. Pevonedistat induces CLL cell apoptosis and circumvented stroma-mediated resistance. Pevonedistat promotes induction of Bim and Noxa in the CLL cells leading to rebalancing of Bcl-2 family members toward the proapoptotic BH3-only proteins. Pevonedistat treatment inhibits overall protein turnover in cultured HCT-116 cells[5]. MLN4924 alone was able to induce cell death in different cell lines that was attributed to apoptosis induction. Also, MLN4924 sensitized different cancer cell lines to TNF-induced cell death. MLN4924/TNF-induced cell death was apoptosis and necroptosis dependent that may be attributed to MLN4924 inhibition of NF-κB pathway activation[6]. Treatment of HCT-116 cells with Pevonedistat for 24 h causes a dose-dependent decrease of Ubc12-NEDD8 thioester and NEDD8-cullin conjugates (IC50 < 0.1 μM) resulting in a reciprocal increase in the abundance of the known CRL substrates CDT1, p27 and NRF2 (also known as NFE2L2), but not non-CRL substrates [7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.08mL

0.42mL

0.21mL

10.42mL

2.08mL

1.04mL

20.83mL

4.17mL

2.08mL
参考文献

[1]Lan H, Tang Z, et al. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218.

[2]Soucy TA, Smith PG, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6.

[3]Teresa A Soucy,et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6.

[4]Soucy TA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6.

[5]J. Claire Godbersen, e tal. The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF-κB Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells. Clin Cancer Res. 2016 Aug 15;22(16):4274.

[6] Mohamed El-Mesery,et al. The NEDD8-activating enzyme inhibition with MLN4924 sensitizes human cancer cells of different origins to apoptosis and necroptosis. Arch Biochem Biophys. 2020 Sep 30;691:108513.

[7]Lan H, et al. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218.