133343-34-7 Usage
Description
LACTACYSTIN is a microbial metabolite isolated from Streptomyces that is widely used as a selective and potent inhibitor of proteasome-mediated degradation of ubiquitin-tagged proteins. It is a Streptomyces metabolite that acts as a highly specific inhibitor of the 20S proteasome (MCP: multicatalytic proteinase complex). 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, leading to the accumulation of ubiquitinated proteins that would normally undergo rapid degradation. The effects of lactacystin are pleiotropic and depend substantially on the expression pattern of signaling proteins within the treated cell. It is a white powder in appearance.
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
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
, 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
Catalytic asymmetric total synthesis of (+)-lactacystin
Fukuda, Nobuhisa,Sasaki, Kazuki,Sastry,Kanai, Motomu,Shibasaki, Masakatsu
, p. 1220 - 1225 (2007/10/03)
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
