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Pevonedistat

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Chemical Structure| 905579-51-3 同义名 : MLN4924
CAS号 : 905579-51-3
货号 : A724332
分子式 : C21H25N5O4S
纯度 : 99%+
分子量 : 443.519
MDL号 : MFCD17215201
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 60 mg/mL(135.28 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
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. Substrates of cullin-RING ligases have important roles in cellular processes associated with cancer cell growth and survival pathways[3]. MLN4924 is a potent and selective inhibitor of NAE with an IC50 value of 0.004 μM[3]. MLN4924 inhibits overall protein turnover in cultured HCT-116 cells. Treatment of HCT-116 cells with MLN4924 for 24 h results in a dose-dependent decrease of Ubc12-NEDD8 thioester and NEDD8-cullin conjugates, with an 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[3]. MLN4924 rapidly inhibits cullin 1 neddylation and remarkably suppresses 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[4]. MLN492410, 30 or 60 mg/kg, s.c. leads to a dose- and time-dependent increase in the steady state levels of NRF2 and CDT1 in HCT-116 tumor-bearing mice, and decreases NEDD8-cullin levels in normal mouse tissue as illustrated in mouse bone marrow cells. MLN4924 administered on a BID schedule at 30 and 60 mg/kg inhibits tumor growth with T/C values of 0.36 and 0.15, respectively[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
K562 cells Proliferation assay 72 h Antiproliferative activity against human K562 cells after 72 hrs by CellTiter-Glo assay, EC50=0.108 μM 24900352
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.27mL

2.25mL

1.13mL

22.55mL

4.51mL

2.25mL
参考文献

[1]Chang PJ, Chen LW, et al. Effects of the NEDD8-Activating Enzyme Inhibitor MLN4924 on Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus. J Virol. 2017 Sep 12;91(19). pii: e00505-17.

[2]Tong S, Si Y, et al. MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma. Sci Rep. 2017 Jul 17;7(1):5599.

[3]Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S, Cullis CA, Doucette A, Garnsey JJ, Gaulin JL, Gershman RE, Lublinsky AR, McDonald A, Mizutani H, Narayanan U, Olhava EJ, Peluso S, Rezaei M, Sintchak MD, Talreja T, Thomas MP, Traore T, Vyskocil S, Weatherhead GS, Yu J, Zhang J, Dick LR, Claiborne CF, Rolfe M, Bolen JB, Langston SP. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6. doi: 10.1038/nature07884. PMID: 19360080.

[4]Lan H, Tang Z, Jin H, Sun Y. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218. doi: 10.1038/srep24218. PMID: 27063292; PMCID: PMC4827092.