905579-51-3

Basic information

• Product Name: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester
• Synonyms: ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)aMino)-7H-pyrrolo[2,3-d]pyriMidin-7-yl)-2-hydroxycyclopentyl)Methyl sulfaMate;[(1S,2S,4R)-4-(4-{[(1S)-2,3-dihydro-1H-inden-1-yl]aMino}-7H-pyrrolo[2,3-d]pyriMidin-7-yl)-2-hydroxycyclopentyl]Methyl sulfaMate;Pevonedistat;MLN4924 (Pevonedistat);Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimi;MLN 4924;Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester
• CAS NO: 905579-51-3
• Molecular Formula: C21H25N5O4S
• Molecular Weight: 443.5193
• Product Categories: Bases & Related Reagents;Carbohydrates & Derivatives;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals
• Mol File: 905579-51-3.mol
• Article Data: 8

Chemical Properties

• Melting Point: 161-163°C
• Boiling Point: 721.0±70.0 °C at 760 mmHg
• Flash Point: 389.9±35.7 °C
• Appearance: White Solid
• Density: 1.62
• Storage Temp.: -20?C Freezer
• Solubility: Soluble in DMSO (up to 10 mg/ml).
• PKA: 9.35±0.70(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester(905579-51-3)
• EPA Substance Registry System: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester(905579-51-3)

Safety Data

• Hazardous Substances Data: 905579-51-3(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 905579-51-3 differently. You can refer to the following data:
1. A potent and selective inhibitor of NAE.
2. 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.

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

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

Upstream product

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• 1281922-73-3 3-tert-butoxy-4-(tert-butyldiphenylsilanyloxymethyl)-cyclopentane-1,2-diol 
• 1281922-76-6 6-(tert-butyldiphenylsilanyloxymethyl)-2,2-dimethyltetrahydrocyclopenta[1,3]dioxol-4-ol 
• 1281922-74-4 6-(tert-butyldiphenylsilanyloxymethyl)-2,2-dimethyltetrahydrocyclopenta[1,3]dioxol-4-one 
• 1281922-72-2 (4-tert-butoxy-2,2-dioxo-tetrahydro-2-yl-6-cyclopenta[1,3,2]-dioxathiol-5-ylmethoxy)-tert-butyl-diphenyl-silane 
• 1281922-85-7 C₂₆H₃₆O₅SSi 
• 945950-17-4 tert-butyl {[((1S,2S,4R)-4-{4-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methoxy]sulfonyl}carbamate 
• 905580-90-7 (1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-(hydroxymethyl)-cyclopentanol 
• 1113025-22-1 [(4S)-4-(tritylamino)cyclopent-1-en-1-yl]methanol 
• 1113025-21-0 methyl (4S)-4-(tritylamino)cyclopent-1-ene-1-carboxylate 
• 1113025-16-3 methyl (1S,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylate 
• 1375958-75-0 (1,4-diazabicyclo[2.2.2]octan-1-ium-1-ylsulfonyl)(tert-butoxycarbonyl)amide 
• 1113025-27-6 (1S,2S,4R)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxylmethyl)cyclopentanol 
• 14052-82-5 4,6-dichloro-5-(2,2-diethoxyethyl)pyrimidine 

Relevant articles and documents

Preparation of Sulfamates and Sulfamides Using a Selective Sulfamoylation Agent

Sulfamates and sulfamides are prevalent in biological molecules, but their universal synthetic methods are limited. We herein report a sulfamoylation agent with high solubility and shelf stability. Various sulfamates and sulfamides can be synthesized directly from alcohols or amines by employing this agent with high selectivity and high yields. This protocol was also successfully used for late-stage sulfamoylation of pharmaceuticals containing a hydroxyl or amino group.

Process Development and GMP Production of a Potent NAE Inhibitor Pevonedistat

A practical synthesis of a novel NEDD8-activating enzyme (NAE) inhibitor pevonedistat (MLN4924) is described. Key steps include an enantioselective synthesis of an amino-diol cyclopentane intermediate containing three chiral centers and a novel, regiosele

Stereoselective synthesis of MLN4924, an inhibitor of NEDD8-activating enzyme

MLN4924 (1), which is in clinical trials as an anticancer agent, was stereoselectively synthesized from d-ribose via a route involving stereoselective reduction, regioselective cleavage of an isopropylidene moiety, and selective displacement of a cyclic s