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

Pevonedistat hydrochloride (Synonyms: MLN4924 (hydrochloride))

Cat. No.: HY-10484 Purity: 98.75%
Handling Instructions

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

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10 mM * 1 mL in DMSO USD 127 In-stock
Estimated Time of Arrival: December 31
1 mg USD 60 In-stock
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5 mg USD 120 In-stock
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10 mg USD 180 In-stock
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50 mg USD 540 In-stock
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100 mg USD 960 In-stock
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200 mg USD 1680 In-stock
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Customer Review

Based on 56 publication(s) in Google Scholar

Other Forms of Pevonedistat hydrochloride:

Top Publications Citing Use of Products

Publications Citing Use of MCE Pevonedistat hydrochloride

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

    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 MCE. Usage Cited in: Elife. 2018 Aug 1;7. pii: e38430.

    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 MCE. Usage Cited in: Elife. 2016 Apr 11;5. pii: e14087.

    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 MCE. Usage Cited in: Ann Hematol. 2014 Sep;93(9):1499-508.

    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

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

    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 MCE. Usage Cited in: Oncotarget. 2016 Jun 14;7(24):35643-35654.

    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 MCE. Usage Cited in: Oncotarget. 2016 Oct 4;7(40):66087-66099.

    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 MCE. Usage Cited in: Oncotarget. 2017 Sep 23;8(49):86395-86409.

    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 MCE. Usage Cited in: Cancer Chemother Pharmacol. 2018 Jun;81(6):1083-1093.

    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 MCE. Usage Cited in: Int J Med Sci. 2018 Apr 3;15(7):674-681.

    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 MCE. Usage Cited in: Nat Commun. 2018 Sep 18;9(1):3801.

    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 MCE. Usage Cited in: Biochem Biophys Res Commun. 2019 Jan 15;508(3):986-990. 

    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 MCE. Usage Cited in: Nat Plants. 2019 Jan;5(1):34-40. 

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

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

    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 MCE. Usage Cited in: Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8273-8280.

    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 MCE. Usage Cited in: Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8273-8280.

    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 MCE. Usage Cited in: Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8273-8280.

    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 MCE. Usage Cited in: Nat Microbiol. 2019 May;4(5):813-825.

    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 MCE. Usage Cited in: Nat Microbiol. 2019 May;4(5):813-825.

    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 MCE. Usage Cited in: Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1070-L1080.

    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 MCE. Usage Cited in: Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1070-L1080.

    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.
    • 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.

    IC50 & Target

    IC50: 4.7 nM (NAE)

    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].

    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].

    Clinical Trial
    Molecular Weight

    479.98

    Formula

    C₂₁H₂₆ClN₅O₄S

    CAS No.

    1160295-21-5

    SMILES

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

    Shipping

    Room temperature in continental US; may vary elsewhere

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (208.34 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
    10 mM 0.2083 mL 1.0417 mL 2.0834 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 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

    • 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

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

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

    *All of the co-solvents are provided by MCE.
    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

    Purity: 98.75%

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    Product Name:
    Pevonedistat hydrochloride
    Cat. No.:
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