Pevonedistat hydrochloride (Synonyms: MLN4924 hydrochloride)

Name: Pevonedistat hydrochloride
Brand: MedChemExpress
SKU: HY-10484
Rating: 5.0 (137 reviews)

Cat. No.: HY-10484 Purity: 99.26%: FAQs
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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

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	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 127	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 60	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 120	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 180	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 540	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 960	In-stock	Estimated Time of Arrival: December 31
200 mg	USD 1680	In-stock	Estimated Time of Arrival: December 31
500 mg		Get quote
1 g		Get quote

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Customer Review

Based on 137 publication(s) in Google Scholar

Other Forms of Pevonedistat hydrochloride:

Pevonedistat In-stock

116 Publications Citing Use of MCE Pevonedistat hydrochloride

IHC

: 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 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 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 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: 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: 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

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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]

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.

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.

1160295-21-5

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
10 mM	0.2083 mL	1.0417 mL	2.0834 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)

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

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: 99.26%

Select Batch:

Data Sheet (284 KB) SDS (0 KB)

COA (255 KB) HNMR (261 KB) RP-HPLC (245 KB) LCMS (110 KB)

Handling Instructions (2659 KB)

References

[1]. Soucy TA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6. [Content Brief]

[2]. J. Claire Godbersen, e tal. The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF-κB Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells. [Content Brief]

[3]. Lan H, et al. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218. [Content Brief]

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	[1]. Soucy TA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6. [Content Brief] [2]. J. Claire Godbersen, e tal. The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF-κB Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells. [Content Brief] [3]. Lan H, et al. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218. [Content Brief]

Complete Stock Solution Preparation Table

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.

Pevonedistat hydrochloride Related Classifications

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:

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

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Pevonedistat hydrochloride (Synonyms: MLN4924 hydrochloride)

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Other Forms of Pevonedistat hydrochloride:

Pevonedistat hydrochloride Related Antibodies

116 Publications Citing Use of MCE Pevonedistat hydrochloride

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References

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Complete Stock Solution Preparation Table

Pevonedistat hydrochloride Related Classifications

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