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Pevonedistat hydrochloride (Synonyms: MLN4924 hydrochloride) 纯度: 98.04%
Pevonedistat hydrochloride (MLN4924 hydrochloride) 是一种有效,选择性的 NEDD8 活化酶 (NEDD8-activating enzyme) 抑制剂,IC50 为 4.7 nM。
Pevonedistat hydrochloride Chemical Structure
CAS No. : 1160295-21-5
规格 | 价格 | 是否有货 | 数量 |
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10 mM * 1 mL in DMSO | ¥1373 | In-stock | |
5 mg | ¥1300 | In-stock | |
10 mg | ¥2092 | In-stock | |
50 mg | ¥5998 | In-stock | |
100 mg | ¥9980 | In-stock | |
200 mg | ¥16500 | In-stock | |
500 mg | 询价 | ||
1 g | 询价 |
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生物活性 |
Pevonedistat hydrochloride (MLN4924 hydrochloride) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor, with an IC50 of 4.7 nM[1]. |
IC50 & Target |
IC50: 4.7 nM (NAE)[1] |
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体外研究 (In Vitro) |
Pevonedistat (MLN4924) is a potent 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). Pevonedistat (MLN4924) treatment inhibits overall protein turnover in cultured HCT-116 cells. Treatment of HCT-116 cells with Pevonedistat (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[1]. 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[2]. 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[3]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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体内研究 (In Vivo) |
Pevonedistat (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 tumour-bearing mice, and decreases NEDD8-cullin levels in normal mouse tissue as illustrated in mouse bone marrow cells. Pevonedistat (MLN4924) administered on a BID schedule at 30 and 60 mg/kg inhibits tumour growth with T/C values of 0.36 and 0.15, respectively[1]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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Clinical Trial |
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分子量 |
479.98 |
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Formula |
C21H26ClN5O4S |
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CAS 号 |
1160295-21-5 |
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运输条件 |
Room temperature in continental US; may vary elsewhere. |
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储存方式 |
4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
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溶解性数据 |
In Vitro:
DMSO : 100 mg/mL (208.34 mM; Need ultrasonic) H2O : 10 mg/mL (20.83 mM; Need ultrasonic) 配制储备液
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
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参考文献 |
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Cell Assay [1] |
HCT-116 cells grown in 6-well cell-culture dishes are treated with 0.1% DMSO (control) or Pevonedistat(MLN4924) for 24 h. Whole cell extracts are prepared and analysed by immunoblotting. For analysis of the E2-UBL thioester levels, lysates are fractionated by non-reducing SDS-PAGE and immunoblotted with polyclonal antibodies to Ubc12, Ubc9 and Ubc10. For analysis of other proteins, lysates are fractionated by reducing SDS-PAGE and probed with primary antibodies as follows: mouse monoclonal antibodies to CDT1, p27, geminin, ubiquitin, securin/PTTG and p53 or rabbit polyclonal antibodies to NRF2, Cyclin B1 and GADD34. Rabbit monoclonal antibodies to NEDD8 and phosphorylated CHK1 (Ser 317) are generated using Ac-KEIEIDIEPTDKVERIKERVEE-amide and Ac-VKYSS(pS)QPEPRT-amide as immunogens, respectively. Antibodies to pH3, cleaved PARP and cleaved caspase 3 are from Cell Signaling Technologies. Secondary HRP-labelled antibodies to rabbit IgG or mouse IgG are used as appropriate. Blots are developed with ECL reagent. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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Animal Administration [1] |
Female athymic NCR mice are used in all in vivo studies. Mice are inoculated with 2×106 HCT-116 cells (or 30-40 mg H522 tumour fragments) subcutaneously in the right flank, and tumour growth is monitored with caliper measurements. When the mean tumour volume reaches approximately 200 mm3, animals are dosed subcutaneously with vehicle (10% cyclodextrin) or Pevonedistat (MLN4924). Inhibition of tumour growth (T/C) is calculated on the last day of treatment. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
参考文献 |
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