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

Pevonedistat hydrochloride  (Synonyms: MLN4924 hydrochloride)

Cat. No.: HY-10484 Purity: 98.81%
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Pevonedistat hydrochloride (MLN4924 hydrochloride) est un inhibiteur de enzyme activant le NEDD8 (NAE) qui est puissant et sélectif, avec un IC50 de 4,7 nM.

Pevonedistat hydrochloride (MLN4924 hydrochloride) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor, with an IC50 of 4.7 nM.

For research use only. We do not sell to patients.

Pevonedistat hydrochloride Chemical Structure

Pevonedistat hydrochloride Chemical Structure

CAS No. : 1160295-21-5

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 127 In-stock
Solution
10 mM * 1 mL in DMSO USD 127 In-stock
Solid
1 mg USD 60 In-stock
5 mg USD 120 In-stock
10 mg USD 180 In-stock
50 mg USD 540 In-stock
100 mg USD 960 In-stock
200 mg USD 1680 In-stock
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Customer Review

Based on 163 publication(s) in Google Scholar

Other Forms of Pevonedistat hydrochloride:

Pevonedistat hydrochloride Related Antibodies

Top Publications Citing Use of Products

142 Publications Citing Use of MCE Pevonedistat hydrochloride

WB
IF
IHC

    Pevonedistat hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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 hydrochloride purchased from MedChemExpress. 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

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    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]
    Cellular Effect
    Cell Line Type Value Description References
    Caco-2 IC50
    0.63 μM
    Compound: PEVONEDISTAT
    Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging
    Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging
    		10.21203/rs.3.rs-23951/v1
    Caco-2 CC50
    222.44 μM
    Compound: PEVONEDISTAT
    Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay
    Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay
    		10.21203/rs.3.rs-23951/v1
    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].

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

    Pevonedistat hydrochloride Related Antibodies
    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].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    Molecular Weight

    479.98

    Formula

    C21H26ClN5O4S
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    O=S(OC[C@H]1[C@H](C[C@@H](C1)N2C=CC3=C(N=CN=C32)N[C@H]4CCC5=C4C=CC=C5)O)(N)=O.Cl
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    4°C, sealed storage, away from moisture

    *In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (208.34 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : 10 mg/mL (20.83 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    * Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

    • Molarity Calculator

    • Dilution Calculator

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

    Mass
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    Concentration
    ×
    Volume
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    Molecular Weight *

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

    =
    Concentration (final)

    C2

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    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

    *In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)

    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.19%

    SDS (252 KB)

    COA (255 KB) HNMR (150 KB) RP-HPLC (248 KB) LCMS (377 KB)

    Handling Instructions (2659 KB)
    References
    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.

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

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

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    H2O / DMSO 1 mM 2.0834 mL 10.4171 mL 20.8342 mL 52.0855 mL
    5 mM 0.4167 mL 2.0834 mL 4.1668 mL 10.4171 mL
    10 mM 0.2083 mL 1.0417 mL 2.0834 mL 5.2086 mL
    15 mM 0.1389 mL 0.6945 mL 1.3889 mL 3.4724 mL
    20 mM 0.1042 mL 0.5209 mL 1.0417 mL 2.6043 mL
    DMSO 25 mM 0.0833 mL 0.4167 mL 0.8334 mL 2.0834 mL
    30 mM 0.0694 mL 0.3472 mL 0.6945 mL 1.7362 mL
    40 mM 0.0521 mL 0.2604 mL 0.5209 mL 1.3021 mL
    50 mM 0.0417 mL 0.2083 mL 0.4167 mL 1.0417 mL
    60 mM 0.0347 mL 0.1736 mL 0.3472 mL 0.8681 mL
    80 mM 0.0260 mL 0.1302 mL 0.2604 mL 0.6511 mL
    100 mM 0.0208 mL 0.1042 mL 0.2083 mL 0.5209 mL

    * Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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    Pevonedistat hydrochloride Related Classifications

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    • 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:

    Pevonedistat1160295-21-5MLN4924MLN 4924MLN-4924NEDD8-activating EnzymeNAEInhibitorinhibitorinhibit

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