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CAS No.: 1160295-21-5

Pevonedistat HCl Catalog No. CSN16306

Synonyms: MLN4924 hydrochloride;Pevonedistat HCl;TAK-924

MLN4924 HCl is a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor (IC50 = 4.7 nM).

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400-920-2911

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技术信息

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].
临床研究

NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT03323034	Recurrent Central Nervous Syst... more >>em Neoplasm Recurrent Lymphoma Recurrent Malignant Solid Neoplasm Refractory Central Nervous System Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Collapse <<	Phase 1	Recruiting	December 1, 2021	-

参考文献

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.0834 mL
- 10.4171 mL
- 20.8342 mL
- 5 mM
- 0.4167 mL
- 2.0834 mL
- 4.1668 mL
- 10 mM
- 0.2083 mL
- 1.0417 mL
- 2.0834 mL

技术信息

CAS号

1160295-21-5

储存条件

粉末: Inert atmosphere,Room Temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C21H26ClN5O4S

运输

蓝冰

分子量

479.98

别名

MLN4924 hydrochloride;Pevonedistat HCl;TAK-924;BAY-73-4506;Pevonedistat

溶解度

DMSO	95.0 mg/mL (197.9 mM) warming
Water	10.0 mg/mL (20.8 mM) warming

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