2. Metabolic Enzyme/Protease
  3. NEDD8-activating Enzyme
  4. Pevonedistat

Pevonedistat  (Synonyms: MLN4924)

目录号: HY-70062 纯度: 99.43%
COA 产品使用指南

摩尔计算器

Pevonedistat (MLN4924) 是一种有效，选择性的NEDD8 活化酶 (NAE) 抑制剂，IC50 为 4.7 nM。

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Pevonedistat Chemical Structure

Pevonedistat Chemical Structure

CAS No. : 905579-51-3

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规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ￥1210
In-stock
1 mg ￥450
In-stock
5 mg ￥1100
In-stock
10 mg ￥1750
In-stock
50 mg ￥4500
In-stock
100 mg 现货 询价
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Customer Review

Other Forms of Pevonedistat:

Pevonedistat 相关抗体

Top Publications Citing Use of Products

MCE 顾客使用本产品发表的 135 篇科研文献

WB
IF
IHC

    Pevonedistat purchased from MCE. Usage Cited in: Nat Microbiol. 2019 May;4(5):813-825.  [Abstract]

    293T cells are treated with MLN4924 and then co-transfected with PSGL-1 and Vpu or an empty vector. One day after the transfection, the cells are treated with CHX and collected at the indicated time points. The cell lysates are analysed by western blotting.

    Pevonedistat purchased from MCE. Usage Cited in: Nat Microbiol. 2019 May;4(5):813-825.  [Abstract]

    293T cells are treated with MLN4924 at the indicated concentrations 24 h before the cells are transfected with plasmids expressing PSGL-1 and Vpu. Two days after transfection, the cells are harvested and analysed by western blotting. Empty vector (–) was used as a negative control for the Vpu- or PSGL-1-expressing vectors.

    Pevonedistat purchased from MCE. Usage Cited in: Nat Plants. 2019 Jan;5(1):34-40.   [Abstract]

    Western analysis of LHCSR1 and LHCSR3 protein expression in the treatment of MLN4924 with different concentrations.

    Pevonedistat purchased from MCE. Usage Cited in: Lab Invest. 2019 Apr;99(4):528-538.  [Abstract]

    Western blot analysis of p65 phosphorylation in synovial cells induced by 100 ng/ml IL-17A with or without 100 nM MLN4924 pretreatment.

    Pevonedistat purchased from MCE. Usage Cited in: Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1070-L1080.  [Abstract]

    Immunoblotting analysis of degradation of IκBα, and levels of p-p65 (also known as RELA) and the NEDD8–Cullin compared with β-actin and total p65 in cell lysates from pulmonary epithelial cells stimulated with rmIL-17A (50 ng/ml) for 15 min after preincubation with the indicated concentration of MLN4924 (MLN) or DMSO for 0.5 h.

    Pevonedistat purchased from MCE. Usage Cited in: Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1070-L1080.  [Abstract]

    Immunoblotting analysis of p-p38, JNK, and ERK compared with total p38, JNK, and ERK in cell lysates from pulmonary epithelial cells stimulated as above.

    Pevonedistat purchased from MCE. Usage Cited in: Biochem Biophys Res Commun. 2019 Jan 15;508(3):986-990.   [Abstract]

    MLN4924 antagonizes the suppressive effects of PTX on cytoskeletal organization in HO8910 and OVA-W cells. (A, C) After treatment with PTX and/or MLN4924 for 48 h, HO8910 and OVA-W cells are stained for α-tubulin and analyzed for intracellular distribution by confocal microscopy. Overlay of blue (nuclei) and red (a-tubulin) channels is shown. (B, D) Levels of α-tubulin protein are further confirmed by western blotting with b-actin as the loading control.

    Pevonedistat purchased from MCE. Usage Cited in: Nat Commun. 2018 Sep 18;9(1):3801.  [Abstract]

    Trophozoites (3D7) are subjected to the indicated treatment for 6 h before analysis of ubiquitinated proteins. Samples treated with MLN4924 are incubated for an additional 3 h prior to DHA treatment. Blots are representative of 3-4 independent experiments.

    Pevonedistat purchased from MCE. Usage Cited in: Elife. 2018 Aug 1;7:e38430.  [Abstract]

    Kelly cells are treated with increasing concentrations of Thal and co-treated with 5 μM Bortezonib, 5 μM MLN4924, 0.5 μM MLN7243, or DMSO as a control. Following 24 h incubation, SALL4 and GAPDH protein levels are assessed by western blot analysis.

    Pevonedistat purchased from MCE. Usage Cited in: Int J Med Sci. 2018 Apr 3;15(7):674-681.  [Abstract]

    NB4 cells are treated with MLN4924 (0, 20, 40 and 80 nM) for 0, 24, 48 and 72 hours, and the protein levels of cullin1 are detected by western blotting, with β-actin used as loading control.

    Pevonedistat purchased from MCE. Usage Cited in: Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8273-8280.  [Abstract]

    AGS cells are transfected with Flag-MRFAP1 for 30 hours and treated with or with 2 μM MLN4924 for additional 4 hours, cells are harvested and subjected to immunoprecipitation with Flag M2 beads and then detected with Western blot.

    Pevonedistat purchased from MCE. Usage Cited in: Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8273-8280.  [Abstract]

    AGS cells are transfected with increased dose of Flag-FBXW8 for 30 hours, 2 μM MLN4924 are added where indicate 4 hours before harvested. Western blot assay is performed with indicated antibodies.

    Pevonedistat purchased from MCE. Usage Cited in: Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8273-8280.  [Abstract]

    MRFAP1 KO AGS cells are treated with or without 2 μM MLN4924 for 24 hours, cells are harvested and subjected to Western blot with indicated antibodies.

    Pevonedistat purchased from MCE. Usage Cited in: Cancer Chemother Pharmacol. 2018 Jun;81(6):1083-1093.  [Abstract]

    786-0 and ACHN cells are treated with MLN4924 (0.5 μM or 1 μM).γ-H2AX is detected by immunoblotting analysis.

    Pevonedistat purchased from MCE. Usage Cited in: Oncotarget. 2017 Oct 12;8(57):97178-97186.  [Abstract]

    After 4 hours 1 µM MLN4924 treatment, lysates from 293T cells stably expressing either Flag or Flag-FBXW8 are immunoprecipitated with anti-FLAG M2 resin. Bound proteins are eluted with FLAG peptide, and all separated cell lysate components are resolved on 10% SDS-PAGE gel, stained by Coomassie Brilliant or subjected to immunoblotting with the indicated antibodies.

    Pevonedistat purchased from MCE. Usage Cited in: Oncotarget. 2017 Sep 23;8(49):86395-86409.  [Abstract]

    Immunofluorescence results, showing that ROC1, DCAF1, DDB1, and TET1 knockdown, and treatment with MLN4924 leads to the reduction of 5hmC levels in A2780 cells. A2780 cells transfected with siNC, siROC1, siDCAF1, siDDB1 or siTET1 and treatment with MLN4924 are subjected to immunofluorescence analysis with antibodies to the indicated protein.

    Pevonedistat purchased from MCE. Usage Cited in: Elife. 2016 Apr 11;5:e14087.  [Abstract]

    Fbxo21-/- RAW264.7 cells are transfected with indicated amounts (0, 1 or 5 μg) Fbxo21-Myc and equal amounts of K29O-Ub-HA vectors for 48 hr, and then infected with VSV (MOI = 1) or HSV-1 (MOI = 5) for 2 hr in the presence or absence of MLN-4924 (10 nM). Then polyubiquitinated ASK1 is examined by immunoblot (IB) against HA after immuneprecipitations (IP).

    Pevonedistat purchased from MCE. Usage Cited in: Technol Cancer Res Treat. 2016 Aug;15(4):527-34.  [Abstract]

    MLN4924 induces accumulation of SCF E3 ligase substrates. Subconfluent cells are treated with MLN4924 (50 nM) or radiation (6 Gy) alone or in combination for 24 hours, followed by immunoblotting (IB) analysis using indicated antibodies.

    Pevonedistat purchased from MCE. Usage Cited in: Oncotarget. 2016 Oct 4;7(40):66087-66099.  [Abstract]

    MLN4924 increases the stability of RORα. MLN4924 increases the half-life of RORα. U2OS cells are transiently transfected with plasmids expressing the Flag-RORα. At 24 h after transfection, MLN4924 (1 μM) or DMSO are added into respective cell culture media. 24 h later, cells are treated with Cycloheximide (CHX) for 0, 3, 6, 4, 9 and 12 h. Equal amounts of whole cell lysates are analyzed by Western blot with a Flag antibody (M2). Actin is used as an internal control.

    Pevonedistat purchased from MCE. Usage Cited in: Oncotarget. 2016 Jun 14;7(24):35643-35654.  [Abstract]

    MLN4924 induces apoptosis is caspase dependent. BMDCs are cultured with MLN4924. Total cellular protein extracts are prepared and subjected to immunoblotting by using A. anti-PARP, anti-caspase-3, anti-caspase-7 antibodies and B. anti-cleaved PARP, anti-cleaved-caspase-3, anti-cleaved-caspase-7 antibodies. C. Caspase-3 activity is examined by caspase activity kit. D. Immunoblotting analysis is performed for erk, p-erk, cyclin D1 and cyclin D3 expression.

    Pevonedistat purchased from MCE. Usage Cited in: Ann Hematol. 2014 Sep;93(9):1499-508.  [Abstract]

    MLN4924-induced p21 high expression eliminates the cell cycle promotion effect of BM-MSCs on Reh cells. a Western blot analysis of p21, skp2, and bax expression in Reh cells treated by different concentration of MLN4924. b Under the treatment of 25 nM IDA, western blot analysis of p21 and skp2 expressions in Reh cells cultured with or without BM-MSCs in the presence of different concentrations of MLN4924 (0, 300, 700 nM). c Under the treatment of 250 nM VP16, western blot analysis of p21 and skp

    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    Pevonedistat (MLN4924) 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]
    体外研究
    (In Vitro)

    Pevonedistat (MLN4924) is a potent inhibitor of NAE, 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) when evaluated in purified enzyme assays that monitor the formation of E2-UBL thioester reaction products. Pevonedistat (MLN4924) selectively inhibits NAE activity compared to the closely related ubiquitin-activating enzyme (UAE, also known as UBA1) and SUMO-activating enzyme (SAE; a heterodimer of SAE1 and UBA2 subunits), in purified enzyme and cellular assays. MLN4924 exhibits potent cytotoxic activity against a variety of human tumour-derived cell lines[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Pevonedistat 相关抗体:
    体内研究
    (In Vivo)

    Pevonedistat (MLN4924) (sc, 10 mg/kg, 30 mg/kg, or 60 mg/kg) inhibits the NEDD8 pathway resulting in DNA damage in Mice bearing HCT-116 xenografts[1].Pevonedistat (sc, 120 mg/kg) and TNF-α (10 μg/kg) synergistically cause liver damage in SD rats[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    分子量

    443.52

    Formula

    C21H25N5O4S
    CAS 号
    性状

    固体

    颜色

    White to light yellow

    运输条件

    Room temperature in continental US; may vary elsewhere.
    储存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    溶解性数据
    细胞实验： 

    DMSO 中的溶解度 : 62.5 mg/mL (140.92 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 2.2547 mL 11.2734 mL 22.5469 mL
    5 mM 0.4509 mL 2.2547 mL 4.5094 mL
    查看完整储备液配制表

    * 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。
    储备液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C储存时，请在2年内使用， -20°C储存时，请在1年内使用。

    • 摩尔计算器

    • 稀释计算器

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    质量
    =
    浓度
    ×
    体积
    ×
    分子量 *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    浓度 (start)

    C1

    ×
    体积 (start)

    V1

    =
    浓度 (final)

    C2

    ×
    体积 (final)

    V2

    动物实验：

    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分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

    • 方案 一

      请依序添加每种溶剂： 10% DMSO    90% Saline

      Solubility: 5 mg/mL (11.27 mM); 悬浊液; 超声助溶

    • 方案 二

      请依序添加每种溶剂： 5% DMSO    95% Saline

      Solubility: 2.5 mg/mL (5.64 mM); 悬浊液; 超声助溶

    动物溶解方案计算器
    请输入动物实验的基本信息：

    给药剂量

    mg/kg

    动物的平均体重

    g

    每只动物的给药体积

    μL

    动物数量

    只
    由于实验过程有损耗，建议您多配一只动物的量
    请输入您的动物体内配方组成：
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    如果您的动物是免疫缺陷鼠或者体弱鼠，建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
    方案所需 助溶剂 包括：DMSO， ，均可在 MCE 网站选购。 ，Tween 80，均可在 MCE 网站选购。
    计算结果
    工作液所需浓度 : mg/mL
    储备液配制方法 : mg 药物溶于 μL  DMSO（母液浓度为 mg/mL）。
    您所需的储备液浓度超过该产品的实测溶解度，以下方案仅供参考，如有需要，请与 MCE 中国技术支持联系。
    动物实验体内工作液的配制方法 : 取 μL DMSO 储备液，加入 μL 。 μL ，混合均匀至澄清，再加 μL Tween 80，混合均匀至澄清，再加 μL 生理盐水。
    连续给药周期超过半月以上，请谨慎选择该方案。
    请确保第一步储备液溶解至澄清状态，从左到右依次添加助溶剂。您可采用超声加热 （超声清洗仪，建议频次 20-40 kHz），涡旋吹打等方式辅助溶解。
    纯度 & 产品资料

    纯度: 99.98%

    COA (198 KB) HNMR (547 KB) RP-HPLC (214 KB) LCMS (109 KB)

    产品使用指南 (1538 KB)
    参考文献
    Cell Assay
    [1]

    HCT-116 cells grown in 6-well cell-culture dishes are treated with 0.1% DMSO (control) or 0.3 μM 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[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1][2]

    Mice[1]
    Mice bearing HCT-116 tumours of 300-500 mm3 are administered a single Pevonedistat (MLN4924) dose (of 10, 30 or 60 mg/kg), and tumors are excised at various time-points over the subsequent 24 h period. The relative levels of NEDD8-cullin and NRF2 are estimated by quantitative immunoblot analysis using Alexa680-labelled anti-IgG as the secondary antibody. The statistical difference between the groups for NEDD8-cullin inhibition is determined using the Kruskal-Wallis test. For the analysis of CDT1 and phosphorylated CHK1 (Ser317) levels in tumour sections, formalin-fixed, paraffin-embedded tumour sections are stained with the relevant antibodies, amplified with HRP-labelled secondary antibodies and detected with the ChromoMap DAB Kit. Slides are counterstained with haematoxylin. Images are captured using an Eclipse E800 microscope and Retiga EXi colour digital camera and processed using Metamorph software. CDT1 and phosphorylated CHK1 levels are expressed as a function of the DAB signal area.
    Rats[2]
    Ten-week-old male Sprague-Dawley rats are used. Across two studies, a total of eight animals in each group are dosed with vehicle, TNF-α, Pevonedistat (MLN4924), or Pevonedistat (MLN4924)+TNF-α. Animals are first intravenously administered either vehicle (1×PBS) or 10 μg/kg TNF-α. One hour later, they are subcutaneously administered vehicle (20% sulfobutyl ether beta-cyclodextrin in 50 mM citrate buffer, pH 3.3) or 120 mg/kg Pevonedistat (MLN4924). Scheduled euthanasia occurred 24 h postdose. Unscheduled euthanasia is performed when animals exhibited moribund conditions. Serum is collected at necropsy and analyzed by Idexx Laboratories for serum chemistry markers of liver damage. Additionally, the livers from five animals in each group are removed, separated into two sections and either frozen at -80°C for subsequent protein analysis or fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 4-6 μm, mounted on glass slides, stained with hematoxylin and eosin, and analyzed with an Olympus BX51 light microscope for histopathology assessment. Microscopic findings are recorded in concordance with the standardized nomenclature for classifying lesions within the livers of rats.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    参考文献

    Pevonedistat 相关分类

    完整储备液配制表

    * 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。
    储备液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C储存时，请在2年内使用， -20°C储存时，请在1年内使用。

    可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.2547 mL 11.2734 mL 22.5469 mL 56.3672 mL
    5 mM 0.4509 mL 2.2547 mL 4.5094 mL 11.2734 mL
    10 mM 0.2255 mL 1.1273 mL 2.2547 mL 5.6367 mL
    15 mM 0.1503 mL 0.7516 mL 1.5031 mL 3.7578 mL
    20 mM 0.1127 mL 0.5637 mL 1.1273 mL 2.8184 mL
    25 mM 0.0902 mL 0.4509 mL 0.9019 mL 2.2547 mL
    30 mM 0.0752 mL 0.3758 mL 0.7516 mL 1.8789 mL
    40 mM 0.0564 mL 0.2818 mL 0.5637 mL 1.4092 mL
    50 mM 0.0451 mL 0.2255 mL 0.4509 mL 1.1273 mL
    60 mM 0.0376 mL 0.1879 mL 0.3758 mL 0.9395 mL
    80 mM 0.0282 mL 0.1409 mL 0.2818 mL 0.7046 mL
    100 mM 0.0225 mL 0.1127 mL 0.2255 mL 0.5637 mL
    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    Pevonedistat905579-51-3MLN4924MLN 4924MLN-4924NEDD8-activating EnzymeNAEInhibitorinhibitorinhibit

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