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Pevonedistat

Catalog No. T6332 CAS 905579-51-3

Synonyms: MLN4924

Pevonedistat (MLN4924) is a potent and selective NEDD8 activating enzyme (NAE) inhibitor (IC50=4.7 nM). Pevonedistat can be used for the treatment of myelodysplastic syndromes (MDS) and also has antitumor activity.

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Pevonedistat, CAS 905579-51-3

Pack Size	Availability	Price/USD
1 mg	In stock	$ 48.00
2 mg	In stock	$ 64.00
5 mg	In stock	$ 97.00
10 mg	In stock	$ 147.00
25 mg	In stock	$ 272.00
50 mg	In stock	$ 446.00
100 mg	In stock	$ 755.00
1 mL * 10 mM (in DMSO)	In stock	$ 95.00

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Purity: 99.92%

Purity: 99.2%

Purity: 99.09%

Purity: 98.21%

Purity: 95%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	Pevonedistat (MLN4924) is a potent and selective NEDD8 activating enzyme (NAE) inhibitor (IC50=4.7 nM). Pevonedistat can be used for the treatment of myelodysplastic syndromes (MDS) and also has antitumor activity.
Targets&IC50	NAE:4.7 nM
In vitro	METHODS: Nine neuroblastoma cell lines were treated with Pevonedistat (12-1000 nM) for 72 h. Cell viability was measured by MTT. RESULTS: All neuroblastoma cell lines tested were sensitive to Pevonedistat with IC50 values ranging from 136-400 nM. [1] METHODS: Human colorectal cancer cells HCT-116 were treated with Pevonedistat (0.001-3 μM) for 24 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: Pevonedistat treatment resulted in a dose-dependent decrease in Ubc12-NEDD8 thioester and NEDD8-cullin couplings, leading to an increase in the abundance of known CRL substrates CDT1, p27 and NRF2. [2]
In vivo	METHODS: To detect anti-tumor activity in vivo, Pevonedistat (30-60 mg/kg in 10% cyclodextrin) was injected subcutaneously into BALB/c mice harboring the human colorectal cancer tumor HCT-116 either once or twice daily for twenty days. RESULTS: Pevonedistat inhibited the growth of HCT-116 xenograft tumors. [2] METHODS: To assay in vivo antitumor activity, Pevonedistat (60 mg/kg, intraperitoneal injection, once daily), venetoclax (50 mg/kg, oral administration, once daily), and azacitidine (8 mg/kg, intravenously three times every seven days) were administered to NSGS mice harboring the AML tumor OCI-AML2-Red- Fluc for fourteen days. RESULTS: Pevonedistat/venetoclax/azacitidine triple therapy induced durable responses in a systemic xenograft model of acute myeloid leukemia. [3]
Kinase Assay	Bcl-2 Binding affinity calculation: A predicted binding affinity for Obatoclax binding to BCL-2 is calculated using the SIE scoring function. [4] As a control in determining the reliability of the calculation, predicted binding affinities Ki) are calculated for a set of 12 small molecules with experimentally measured binding affinities to BCL-2.
Cell Research	MLN4924 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. HCT-116 cells grown in 6-well cell-culture dishes are treated with 0.1% DMSO (control) or 0.3 μM 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].

Synonyms	MLN4924
Molecular Weight	443.52
Formula	C21H25N5O4S
CAS No.	905579-51-3

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 125 mg/mL (281.83 mM）, Sonication is recommended.

References and Literature

1. Foster JH, et al. The Anti-Tumor Activity of the NEDD8 Inhibitor Pevonedistat in Neuroblastoma. Int J Mol Sci. 2021 Jun 18;22(12):6565. 2. 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. 3. Cojocari D, et al. Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia. Haematologica. 2022 Apr 1;107(4):825-835. 4. Chen S M, Lin T K, Tseng Y Y, et al. Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21[J]. Cancer medicine. 2018 Aug;7(8):3988-4003. 5. Qin Z, Hu H, Sun W, et al. miR-224-5p Contained in Urinary Extracellular Vesicles Regulates PD-L1 Expression by Inhibiting Cyclin D1 in Renal Cell Carcinoma Cells. Cancers . 2021, 13, 618[J]. 2021.

Citations

1. Qin Z, Hu H, Sun W, et al. miR-224-5p Contained in Urinary Extracellular Vesicles Regulates PD-L1 Expression by Inhibiting Cyclin D1 in Renal Cell Carcinoma Cells. Cancers. 2021 Feb 4;13(4):618. doi: 10.3390/cancers13040618. 2. Hussain M, Lu Y, Tariq M, et al. A small-molecule Skp1 inhibitor elicits cell death by p53-dependent mechanism. Iscience. 2022, 25(7): 104591. 3. Chen S M, Lin T K, Tseng Y Y, et al. Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21. Cancer Medicine. 2018 Aug;7(8):3988-4003 4. Fu Z, Liao W, Ma H, et al. Inhibition of neddylation plays protective role in lipopolysaccharide-induced kidney damage through CRL-mediated NF-κB pathways. Am J Transl Res. 2019, 11(5): 2830-2842 5. Sun Y, Baechler S A, Zhang X, et al.Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex.Nature Communications.2023, 14(1): 3762. 6. Zhong C, Zhu R, Jiang T, et al.Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple‐Negative Breast Cancer.Advanced Science.2023: 2305035.

Related compound libraries

This product is contained In the following compound libraries：

Anti-Cancer Active Compound Library Drug Repurposing Compound Library Anti-Cancer Drug Library Inhibitor Library Anti-Cancer Clinical Compound Library HIF-1 Signaling Pathway Compound Library Metabolism Compound Library Clinical Compound Library Fluorochemical Library Anti-Liver Cancer Compound Library

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Keywords

Pevonedistat 905579-51-3 Metabolism Ubiquitination NEDD8 E1/E2/E3 Enzyme NEDD8-activating Enzyme MLN-4924 MLN4924 Inhibitor MLN 4924 inhibit NAE inhibitor

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