Pevonedistat (Synonyms: MLN4924)

Name: Pevonedistat
Brand: MedChemExpress
SKU: HY-70062
Rating: 5.0 (158 reviews)

Cat. No.: HY-70062 Purity: 99.43%: FAQs
Data Sheet SDS COA Handling Instructions

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Pevonedistat (MLN4924) 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 Chemical Structure

CAS No. : 905579-51-3

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 117	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 117	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 158 publication(s) in Google Scholar

Other Forms of Pevonedistat:

Pevonedistat hydrochloride In-stock

137 Publications Citing Use of MCE Pevonedistat

IHC

: Pevonedistat 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 (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]

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].

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

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].

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

Clinical Trial

Molecular Weight

443.52

Formula

C₂₁H₂₅N₅O₄S

CAS No.

905579-51-3

Appearance

Solid

Color

White to light yellow

SMILES

O=S(OC[C@@H]1C[C@@H](N2C3=NC=NC(N[C@H]4CCC5=C4C=CC=C5)=C3C=C2)C[C@@H]1O)(N)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 62.5 mg/mL (140.92 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	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
10 mM	0.2255 mL	1.1273 mL	2.2547 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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 90% Saline
Solubility: 5 mg/mL (11.27 mM); Suspended solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 5% DMSO 95% Saline
Solubility: 2.5 mg/mL (5.64 mM); Suspended solution; Need ultrasonic
Protocol 3

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (4.69 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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 4

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (4.69 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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 5

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (4.69 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 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 (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 6

Add each solvent one by one: 1% DMSO 99% Saline
Solubility: 0.5 mg/mL (1.13 mM); Suspended solution; Need ultrasonic

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).

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: 99.98%

Select Batch:

Data Sheet (283 KB) SDS (393 KB)

COA (254 KB) HNMR (547 KB) RP-HPLC (214 KB) LCMS (109 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]. F S Wolenski, et al. The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-α to activate apoptosis. Cell Death Discovery 1, Article number: 15034 (2015)

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.
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]. F S Wolenski, et al. The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-α to activate apoptosis. Cell Death Discovery 1, Article number: 15034 (2015)

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	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

Pevonedistat 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:

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

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Pevonedistat (Synonyms: MLN4924)

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Other Forms of Pevonedistat:

Pevonedistat Related Antibodies

137 Publications Citing Use of MCE Pevonedistat

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Pevonedistat Related Antibodies

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Complete Stock Solution Preparation Table

Pevonedistat Related Classifications

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