133343-34-7

Usage

Uses

Used in Pharmaceutical Industry:
LACTACYSTIN is used as a proteasome inhibitor for inhibiting protein degradation, which has potential applications in the development of therapeutic strategies for various diseases, including cancer.
Used in Research Applications:
LACTACYSTIN is used as a research tool to inhibit proteasomal activity of cells for live cell imaging, allowing researchers to study the effects of proteasome inhibition on cellular processes.
Used in Immunology:
LACTACYSTIN is used to block proteasomal proteolysis in human monocyte-derived dendritic cells (MoDCs) for 24 hours, which can help in understanding the role of proteasomes in immune cell function.
Used in Neuroscience:
LACTACYSTIN is used to provide unilateral injection to animals to induce nigrostriatal lesions, which can be useful in studying the effects of proteasome inhibition on neurodegenerative diseases such as Parkinson's disease.

Biochem/physiol Actions

Lactacystin can block the development of cell cycle and stimulate differentiation in a murine neuroblastoma cell line. It can serve as a precursor for?clasto-lactacystin β-lactone. Cell-permeable and irreversible proteasome inhibitor (Ki = 4nM). Inhibits NF-kB activation (IC50 = 10mM). Induces neurite outgrowth in neuro2A mouse neuroblastoma cells.

References

1) Omura et al. (1991), Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells; J. Antibiot., 44 113 2) Fenteany et al. (1995), Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin; Science, 268 726

InChI:InChI=1/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)/t7-,9+,10+,11+,15-/m1/s1

Upstream product

• 616-91-1 N-acetylcystein 
• 154226-60-5 omuralide 
• 895579-09-6 (3S,4S,7R,8S)-8-Hydroxy-3-isopropyl-7-methyl-2-oxa-5-aza-spiro[3.4]octane-1,6-dione 
• 216449-93-3 (4aS,7R,7aS)-tetrahydro-4a-(hydroxymethyl)-2,2,7-trimethyl[1,3]dioxino[5,4-b]pyrrol-6(4H)-one 
• 216449-95-5 (3R,4S)-4-Hydroxy-3,8,8-trimethyl-7,9-dioxa-1-aza-spiro[4.5]decan-2-one 
• 1027314-00-6 (4aS,7R,7aS)-2,2,7-Trimethyl-6-oxo-tetrahydro-[1,3]dioxino[5,4-b]pyrrole-4a-carboxylic acid 
• 216449-97-7 methyl (4aS,7R,7aS)-hexahydro-2,2,7-trimethyl-6-oxo-[1,3]dioxino[5,4-b]pyrrole-4a-carboxylate 
• 216449-99-9 (4aR,7R,7aS,1'S)-tetrahydro-4a-(1'-hydroxy-2'-methylpropyl)-2,2,7-trimethyl[1,3]dioxino[5,4-b]pyrrol-6(4H)-one 
• 203934-88-7 (2R,3S)-3-[(4S,5S)-3-Benzyl-4-(tert-butyl-dimethyl-silanyloxymethyl)-5-isopropyl-oxazolidin-4-yl]-3-hydroxy-2-methyl-propionic acid methyl ester 
• 145451-91-8 (2R,3S)-2-Benzylamino-3-hydroxy-2-hydroxymethyl-4-methyl-pentanoic acid methyl ester 
• 928209-79-4 2-(1-acetoxy-2-methyl-propyl)-3-hydroxy-4-methyl-5-oxo-pyrrolidine-2-carboxylic acid methyl ester 
• 928209-77-2 (2R,3S)-1-tert-butyl 2-methyl 2-((S)-1-acetoxy-2-methylpropyl)-3-hydroxy-5-oxopyrrolidine-1,2-dicarboxylate 
• 928209-78-3 2-(1-acetoxy-2-methyl-propyl)-3-hydroxy-4-methyl-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 1334590-08-7 (2R,3S)-1-tert-butyl 2-methyl 2-((S)-1-acetoxy-2-methylpropyl)-3-(tert-butyldimethylsilyloxy)-5-oxopyrrolidine-1,2-dicarboxylate 

Relevant academic research and scientific papers

A concise route to (+)-lactacystin

A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3- dioxan-5-ylcarbamate, e

SYNTHESIS OF (6R,7S)-LACTACYSTIN AND 6-DEOXYLACTACYSTIN FROM A COMMON INTERMEDIATE

The stereocontrolled syntheses of (6R,7S)-lactacystin and deoxylactacystin, analogs of the neurotrophic agent lactacystin, are described.

Application of Two Direct C(sp3)-H Functionalizations for Total Synthesis of (+)-Lactacystin

(Figure Presented). Herein, we report a new synthetic route from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome. The photoinduced intermolecular C(sp3)-H alkynylation and intramolecular C(sp3)-H acylation chemo- and stereoselectively constructed the tetra- and trisubstituted carbon centers, respectively. The obtained bicycle was transformed into the target compound in a concise manner. The present total synthesis demonstrates the power of the direct C(sp3)-H functionalizations for the assembly of multiple functionalized structures of natural products.

Stereospecific total syntheses of proteasome inhibitors omuralide and lactacystin

Omuralide, a transformation product of the microbial metabolite lactacystin, was the first molecule discovered as a specific inhibitor of the proteasome and is unique in that it specifically inhibits the proteolytic activity of the 20S subunit of the prot

Enantioselective total syntheses of omuralide, 7-epi-omuralide, and (+)-lactacystin

(Chemical Equation Presented) An alkylidene carbene 1,5-CH insertion has been used as a key step in an enantioselective total syntheses of omuralide, its C7-epimer, and (+)-lactacystin. An additional noteworthy feature of the synthesis is the use of a nov

α,β-unsaturated β-silyl lmide substrates for catalytic, enantioselective conjugate additions: A total synthesis of (+)-lactacystin and the discovery of a new proteasome inhibitor

Chiral (salen)Al μ-oxo dimer 1 catalyzes the highly enantioselective conjugate addition of carbon-centered nucleophiles to α,β-unsaturated silyl imides. Allyldimethylsilane-substituted imide 4 was identified as an optimal substrate, undergoing addition re

Catalytic asymmetric total synthesis of (+)-lactacystin

Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor, was accomplished using a catalytic enantioselective Strecker reaction of a ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was selected as a sta

Lactacystin analogs

Compounds related to lactacystin and lactacystin Beta-lactone, pharmaceutical compositions containing the compounds, and methods of use.

Total synthesis of (+)-lactacystin

A double stereodifferentiating crotylation between aldehyde 1 and silane (S)-2 to afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn > 30:1) in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a metabolite isol

Lactacystin analogs

Described herein are compounds related to lactacystin and lactacystin β-lactone, pharmaceutical compositions containing the compounds, and methods of use.