437742-34-2

Basic information

• Product Name: MarizoMib
• Synonyms: MarizoMib;(-)-SalinosporaMide A;ML 858;NPI 0052;SalinosporaMide A;MarizoMib (NPI-0052, (-)-SalinosporaMide A);Marizomib (Salinosporamide A);(1S,2R,5R)-2-(2-chloroethyl)-5-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-1-methyl-7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione
• CAS NO: 437742-34-2
• Molecular Formula: C₁₅H₂₀ClNO₄
• Molecular Weight: 313.7766
• Mol File: 437742-34-2.mol
• Article Data: 18

Chemical Properties

• Boiling Point: 547.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.348±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO
• PKA: 13.10±0.20(Predicted)
• CAS DataBase Reference: MarizoMib(CAS DataBase Reference)
• NIST Chemistry Reference: MarizoMib(437742-34-2)
• EPA Substance Registry System: MarizoMib(437742-34-2)

Safety Data

• RTECS: RN6803500
• Hazardous Substances Data: 437742-34-2(Hazardous Substances Data)

Usage

Uses

Marizomib has been used as a proteasome inhibitor:to study its effects on glioblastoma cell linesto analyze its effects on the aging of killifish brainto test its effect on protein kinase B (PKB/AKT) levels in multiple myeloma cells

Definition

ChEBI: A salinosporamide in which the core (1R)-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione skeleton is substituted at positions 1, 4, and 5 by (1S)-cyclohex-2-en-1-yl(hydroxy)methyl, 2-chloroethyl, and methyl groups, respectively (the 1R,4R,5S diastereoisomer). A potent proteasome inhibitor, it has attracted interest for potential use in the treatment of various cancers.

Biological Activity

salinosporamide a is a potent inhibitor of 20s proteasome with ic50 value of 1.3 nm [1].salinosporamide a was isolated from the crude extract of a salinospora strain cnb-392. it showed potent anti-tumor activity with an ic50 value of 11 ng/ml in hct-116 cells. it also exerted a mean gi50 value of less than 10 nm in the nci’s 60 cell line-panel. among these cell lines, salinosporamide a showed the greatest potent efficacies in nci-h226, sf-539, sk-mel-28 and mda-mb-435 cells. salinosporamide a inhibited the purified 20s proteasome with ic50 value of 1.3 nm. it was about 35-fold more potent than the first discovered specific proteasome inhibitor, omuralide [1].

Biochem/physiol Actions

Marizomib is a second generation proteasome inhibitor with anti-cancer activity. Marizomib binds irreversibly and potently inhibits all three 20S proteasome subunits.

references

[1] feling r h, buchanan g o, mincer t j, et al. salinosporamide a: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. angewandte chemie international edition, 2003, 42(3): 355-357.

Upstream product

• 872360-17-3 NPI-2062 
• 9005-25-8 starch 
• 1064062-25-4 (1S,2R,5R)-2-(2-chloroethyl)-5-{(S)-[(S)-cyclohex-2-enyl](triethylsilyloxy)methyl}-1-methyl-7-oxa-4-aza-bicyclo[3.2.0]heptane-3,6-dione 
• 1239897-07-4 C₁₇H₂₀ClNO₅ 
• 1256638-99-9 C₂₃H₂₈ClNO₅ 
• 1258864-02-6 C₁₉H₂₀ClNO₄ 
• 1258864-01-5 C₁₇H₁₈ClNO₃ 
• 1258864-00-4 C₁₇H₂₀ClNO₄ 
• 1258863-99-8 C₁₆H₂₀ClNO₃ 
• 949573-73-3 C₁₅H₂₂ClNO₅ 
• 704910-41-8 (2R,3S,4R)-2-[(S)-{(S)-cyclohex-2-enyl}hydroxymethyl]-3-hydroxy-4-(2-hydroxyethyl)-1-(4-methoxybenzyl)-3-methyl-5-oxopyrrolidine-2-carboxylic acid methyl ester 
• 704910-44-1 (3R,3aS,7aR)-3-Hydroxymethyl-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester 
• 704910-38-3 (3S,3aS,7aR)-3-Formyl-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester 
• 704910-42-9 (2R,3S,4R)-2-((S)-(S)-Cyclohex-2-enyl-hydroxy-methyl)-3-hydroxy-4-(2-hydroxy-ethyl)-3-methyl-5-oxo-pyrrolidine-2-carboxylic acid methyl ester 

Downstream Products

• 949573-73-3 C₁₅H₂₂ClNO₅ 
• 1078636-12-0 C₁₆H₂₀N₂O₄S 
• 872360-18-4 NPI-2076 

Relevant articles and documents

A Total Synthesis of Salinosporamide A

Salinosporamide A is a β-lactone proteasome inhibitor currently in clinical trials for the treatment of multiple-myeloma. Herein we report a short synthesis of this small, highly functionalized, biologically important natural product that uses an oxidative radical cyclization as a key step and allows for the preparation of gram quantities of advanced synthetic intermediates.

Preparation method and application of Marizomib key intermediate

The invention belongs to the field of chemical synthesis, particularly relates to a preparation method and application of a Marizomib key intermediate, and particularly relates to a preparation methodof a Marizomib key intermediate. Natural L-serine is selected as an initial raw material, and an obtained serine fragment protected by a functional group is connected with a 1, 3-dicarbonyl cyclopropyl compound so that the Marizomib key intermediate (a skeleton structure) is prepared, and the preparation method is high in preparation efficiency and yield, safer and more environmentally friendly.Then, the prepared Marizomib key intermediate is used for producing Marizomib, and the Marizomib is obtained through intramolecular cyclization reaction and group modification, protective group removal and structural modification in sequence. Besides, the low-toxicity solvent is used in the whole synthesis process, reagents with high toxicity and difficult preparation are avoided, the solvent consumption is low, the target product recovery rate is high and the stability is good.

Total synthesis of (-)-salinosporamide A

A concise and stereoselective total synthesis of (-)-salinosporamide A (1), a potent inhibitor of the 20S proteasome that is in clinical development as an anticancer drug candidate, has been accomplished in 14 steps with 19% overall yield from 4-pentenoic acid. Our synthesis features a stereoselective alkylation utilizing a chiral auxiliary, formation of a pyrrolidine unit, and oxidation of the pyrrolidine to a γ-lactam. To demonstrate the scalability of our synthesis, (-)-salinosporamide A has been synthesized on a gram scale.