Pevonedistat
- CAS No.
- 905579-51-3
- Chemical Name:
- Pevonedistat
- Synonyms
- MLN 4924;CS-821;TAK-924;Pevonedistat;mln4924 Free Base;PEVONEDISTAT;MLN-4924;MLN4924 (Pevonedistat);Pevonedistat (TAK-924);Pevonedistat (MLN-4924,TAK 924);Pevonedistat ISO 9001:2015 REACH
- CBNumber:
- CB92510096
- Molecular Formula:
- C21H25N5O4S
- Molecular Weight:
- 443.52
- MDL Number:
- MFCD17215201
- MOL File:
- 905579-51-3.mol
- MSDS File:
- SDS
Melting point | 161-163°C |
---|---|
Boiling point | 721.0±70.0 °C(Predicted) |
Density | 1.62 |
storage temp. | -20°C Freezer |
solubility | Soluble in DMSO (up to 10 mg/ml). |
form | solid |
pka | 9.35±0.70(Predicted) |
color | White |
Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months. |
NCI Dictionary of Cancer Terms | pevonedistat |
FDA UNII | S3AZD8D215 |
NCI Drug Dictionary | pevonedistat |
SAFETY
Risk and Safety Statements
Symbol(GHS) | GHS07 |
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Signal word | Warning | |||||||||
Hazard statements | H315-H319 | |||||||||
Precautionary statements | P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 | |||||||||
NFPA 704 |
|
Pevonedistat price More Price(33)
Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
---|---|---|---|---|---|---|---|
Cayman Chemical | 15217 | MLN4924 ≥98% | 905579-51-3 | 1mg | $49 | 2024-03-01 | Buy |
Cayman Chemical | 15217 | MLN4924 ≥98% | 905579-51-3 | 5mg | $96 | 2024-03-01 | Buy |
Cayman Chemical | 15217 | MLN4924 ≥98% | 905579-51-3 | 10mg | $168 | 2024-03-01 | Buy |
Tocris | 6499 | MLN4924 ≥98%(HPLC) | 905579-51-3 | 10 | $139 | 2021-12-16 | Buy |
TRC | M425100 | MLN4924 | 905579-51-3 | 1mg | $90 | 2021-12-16 | Buy |
Pevonedistat Chemical Properties,Uses,Production
Description
MLN4924 (905579-51-3) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor.1?It disrupts cullin-RING ligase-mediated protein turnover leading to apoptosis in human tumor cells. Suppresses the growth of human tumor xenografts in mice.2?Upregulates PD-L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma.3?Modulates tumor microenvironment.4?Cell permeable.
Chemical Properties
White Solid
Uses
A potent and selective inhibitor of NAE. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. The ubiquitin-proteasome pathway mediates the destruction of unwanted proteins. Potent NAE inhibitor; NEDD8 E1 Activating Enzyme Inhibitor.
Definition
ChEBI: Pevonedistat is a pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes. It has a role as an apoptosis inducer and an antineoplastic agent. It is a pyrrolopyrimidine, a secondary amino compound, a member of cyclopentanols, a sulfamidate and a member of indanes.
Enzyme inhibitor
This first-in-class small molecule inhibitor (FW = 443.52 g/mol; CAS 905579-51-3; Solubility = 10 mg/mL DMSO), also named MLN4924 and [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3- d]pyrimidin-7-yl]-2-hydroxycyclopentyl]sulfamate methyl ester, targets Nedd8 activating enzyme, or NAE (IC50 = 4.7 nM), with much weaker action against UAE (IC50 = 1.5 μM), SAE (IC50 = 8.2 μM), and UBA6 (IC50 = 1.8 μM). In most cancer cells, pevonedistat treatment results in the induction of DNA re-replication, resulting in DNA damage and cell death. MLN4924 also exhibits an alternative mechanism of action. Treatment of activated B cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) cells with pevonedistat resulted in rapid accumulation of pIkBa, decrease in nuclear p65 content, reduction of transcriptional activity of NF-kB (or nuclear factor k-light-chain-enhancer of activated B cells), and G1 arrest, ultimately resulting in apoptosis induction, events consistent with potent NF-kB pathway inhibition. Treatment of germinal-center B cell-like (GCB) DLBCL cells resulted in an increase in cellular Cdt-1 and accumulation of cells in S-phase, consistent with cells undergoing DNA rereplication. Pevonedistat also inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin-ligase and blocking SIVmac replication in myeloid cells, therebyindicating the potential efficacy of inhibiting neddylation as an antiretroviral strategy
storage
Store at -20°C
References
1) Soucy, et al. (2009), An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458 732 2) Milhollen, et al. (2010) MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-(kappa)B-dependent lymphoma. Blood, 116 1515 3) Zhou et al. (2019) Neddylation inhibition upregulates PD-L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma; Int. J. Cancer, 145 763 4) Zhou et al. (2019) Neddylation: a novel modulator of the tumor microenvironment; Mol. Cancer 18 77
Pevonedistat Preparation Products And Raw materials
Raw materials
Preparation Products
Supplier | Tel | Country | ProdList | Advantage | |
---|---|---|---|---|---|
Wuhan Haorong Biotechnology Co.,ltd | +86-18565342920; +8618565342920 | sales@chembj.net | China | 289 | 58 |
Nanjing ChemLin Chemical Industry Co., Ltd. | 025-83697070 | product@chemlin.com.cn | CHINA | 3012 | 60 |
ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32760 | 60 |
Hubei xin bonus chemical co. LTD | 86-13657291602 | linda@hubeijusheng.com | CHINA | 22968 | 58 |
BOC Sciences | +1-631-485-4226 | inquiry@bocsci.com | United States | 19553 | 58 |
Chongqing Chemdad Co., Ltd | +86-023-6139-8061 +86-86-13650506873 | sales@chemdad.com | China | 39916 | 58 |
CONIER CHEM AND PHARMA LIMITED | +8618523575427 | sales@conier.com | China | 49391 | 58 |
Career Henan Chemica Co | +86-0371-86658258 +8613203830695 | laboratory@coreychem.com | China | 30250 | 58 |
Dideu Industries Group Limited | +86-29-89586680 +86-15129568250 | 1026@dideu.com | China | 24330 | 58 |
Finetech Industry Limited | +86-27-87465837 +8618971612321 | info@finetechnology-ind.com | China | 9602 | 58 |
View Lastest Price from Pevonedistat manufacturers
Image | Update time | Product | Price | Min. Order | Purity | Supply Ability | Manufacturer | |
---|---|---|---|---|---|---|---|---|
2024-08-26 | Pevonedistat
905579-51-3
|
US $0.00-0.00 / KG | 1KG | 99% | 5000 | Wuhan Haorong Biotechnology Co.,Ltd | ||
2022-08-31 | Pevonedistat
905579-51-3
|
US $1.10 / g | 1g | 99.00% | 100 Tons Min | Dideu Industries Group Limited | ||
2021-01-06 | Pevonedistat
905579-51-3
|
US $1.00 / g | 1g | 85.0-99.8% | 20tons | Career Henan Chemica Co |
- Pevonedistat
905579-51-3
- US $0.00-0.00 / KG
- 99%
- Wuhan Haorong Biotechnology Co.,Ltd
- Pevonedistat
905579-51-3
- US $1.10 / g
- 99.00%
- Dideu Industries Group Limited
- Pevonedistat
905579-51-3
- US $1.00 / g
- 85.0-99.8%
- Career Henan Chemica Co