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| 5mg |
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| 25mg |
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Purity: ≥98%
Pevonedistat (previously known as MLN-4924; TAK-924) is a potent and selective small molecule inhibitor of Nedd8 (Neural precursor cell expressed, developmentally down-regulated 8) activating enzyme (NAE) with anticancer activity. It inhibits NAE with IC50 of 4 nM. Pevonedistat 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. By binding to and inhibiting NAE, Pevonedistat can inhibit tumor cell proliferation and survival. NAE activates Nedd8, an ubiquitin-like (UBL) protein that modifies cellular targets in a pathway that is parallel to but distinct from the ubiquitin-proteasome pathway (UPP).
| ln Vitro |
In purified enzyme assays that track the formation of E2-UBL thioester reaction products, pevonedistat (MLN4924) is a potent inhibitor of NAE and selective against the closely related enzymes UAE, SAE, UBA6, and ATG7 (IC50=1.5, 8.2, 1.8, and >10 μM, respectively). In pure enzyme and cellular assays, pevonedistat (MLN4924) preferentially inhibits NAE activity in contrast to the closely related ubiquitin-activating enzyme (UAE, also known as UBA1) and SUMO-activating enzyme (SAE; a heterodimer of SAE1 and UBA2 subunits). Strong cytotoxic activity is demonstrated by MLN4924 against several human tumor-derived cell lines[1].
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| ln Vivo |
In mice carrying HCT-116 xenografts, pevonedistat (MLN4924) (sc, 10 mg/kg, 30 mg/kg, or 60 mg/kg) inhibits the NEDD8 pathway, causing DNA damage[1]. The combination of pevonedistat (sc, 120 mg/kg) and TNF-α (10 μg/kg) damages the livers of SD rats[2].
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| 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.
[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) |
| Molecular Formula |
C21H25N5O4S
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| Molecular Weight |
443.52
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| CAS # |
905579-51-3
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| Related CAS # |
Pevonedistat hydrochloride;1160295-21-5
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| SMILES |
O=S(OC[ C@H]1[C@@H](O)C[ C@H](N2C=CC3=C(N[ C@H]4CCC5=C4C=CC=C5)N=CN=C32)C1)(N)=O
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (11.27 mM) (saturation unknown) in 10% DMSO + 90% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.64 mM) (saturation unknown) in 5% DMSO + 95% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.08 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: 1% DMSO 99% Saline |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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 Pevonedistat+TNF-αis cytotoxic.Cell Death Discovery 1, Article number: 15034 (2015) |
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 Pevonedistat+TNF-αdrives caspase-8 activation and p10 accumulation.Cell Death Discovery 1, Article number: 15034 (2015) |
 Combination of pevonedistat and elevated TNF-αis toxic to rats.Cell Death Discovery 1, Article number: 15034 (20 |
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