133343-34-7 Usage
Description
Lactacystin is a microbial metabolite isolated from Streptomyces that is now widely used as a selective inhibitor of the 20S proteasome. Lactacystin was first characterized by its ability to induce differentiation and inhibit cell cycle progression in several tumor cell lines. At concentrations from 2 to 10 μM, lactacystin induces the outgrowth of neurites in the neuroblastoma cell line Neuro2a. Lactacystin irreversibly alkylates subunit X of the 20S proteasome. The concomitant inhibition of proteasome peptidase activity results in the accumulation of a variety of ubiquitinated proteins which would normally undergo rapid degradation. Thus, the effects of lactacystin are pleiotropic and depend substantially on the expression pattern of signalling proteins within the treated cell.
Chemical Properties
White Powder
Uses
Different sources of media describe the Uses of 133343-34-7 differently. You can refer to the following data:
1. A selective and potent inhibitor of proteasome-mediated degradation of ubiquitin-tagged proteins. A Streptomyces metabolite that acts as a highly specific inhibitor of the 20S proteasome (MCP: multicatalytic proteinase complex)
2. Lactacystin has been used:as a proteasome inhibitor to inhibit protein degradationto inhibit proteasomal activity of cells for live cell imagingto block proteasomal proteolysis in human monocyte-derived dendritic cells (MoDCs) for 24 hto provide unilateral injection to animals to induce nigrostriatal lesions
Definition
ChEBI: L-Cysteine substituted at nitrogen by an acetyl group and at sulfur by a substituted-lactam carbonyl group.
General Description
Lactacystin is an antibiotic?and a metabolite of Streptomyces?spp.
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
Check Digit Verification of cas no
The CAS Registry Mumber 133343-34-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,3,3,4 and 3 respectively; the second part has 2 digits, 3 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 133343-34:
(8*1)+(7*3)+(6*3)+(5*3)+(4*4)+(3*3)+(2*3)+(1*4)=97
97 % 10 = 7
So 133343-34-7 is a valid CAS Registry Number.
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
133343-34-7Relevant articles and documents
A concise route to (+)-lactacystin
Ooi, Hidenori,Ishibashi, Norihisa,Iwabuchi, Yoshiharu,Ishihara, Jun,Hatakeyama, Susumi
, p. 7765 - 7768 (2004)
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
Application of Two Direct C(sp3)-H Functionalizations for Total Synthesis of (+)-Lactacystin
Yoshioka, Shun,Nagatomo, Masanori,Inoue, Masayuki
supporting information, p. 90 - 93 (2015/07/28)
(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.
Enantioselective total syntheses of omuralide, 7-epi-omuralide, and (+)-lactacystin
Hayes, Christopher J.,Sherlock, Alexandra E.,Green, Martin P.,Wilson, Claire,Blake, Alexander J.,Selby, Matthew D.,Prodger, Jeremy C.
, p. 2041 - 2051 (2008/09/19)
(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
Balskus, Emily P.,Jacobsen, Eric N.
, p. 6810 - 6812 (2007/10/03)
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