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Key inhibitor for use in proteasome research.
A potent and selective irreversible proteasome inhibitor. Specifically inhibits 20S proteasome (MCP; multicatalytic complex). Blocks proteasome activity by targeting the catalytic β-subunit. Has no effect on serine or cysteine proteases. Induces apoptosis inhuman monoblast U937 cells. Inhibits NF-κB activation by inhibiting IκB degradation (IC50=10 µM). Inhibits the ubiquitin proteasome pathway in cell culture. Inhibits cathepsin A. Upregulates HSP70 and HSP22, suggesting an initial neuroprotective pathway. Induces neurite outgrowth in Neuro 2A mouse neuroblastoma cells.
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Product Details
| Appearance |
White to off-white solid. |
|---|---|
| CAS |
133343-34-7 |
| Couple Target |
Proteasome 26S |
| Couple Type |
Inhibitor |
| Formula |
C15H24N2O7S |
| Identity |
Determined by 1H-NMR and MS. |
| MW |
376.4 |
| Purity |
≥97% (HPLC) |
| Solubility |
Soluble in water (10mg/ml), 100% ethanol (1mg/ml), methanol, DMSO (20mg/ml), dimethyl formamide (20mg/ml) or acetonitrile (20mg/ml). |
| Source |
Synthetic |
Handling & Storage
| Use/Stability |
As indicated on product label or CoA when stored as recommended. Organic stock solutions are stable for 3 months when stored at -20°C. Subject to hydrolysis in aqueous buffers. We do not recommend storing aqueous solutons for more than one day. |
|---|---|
| Handling |
Protect from light. Avoid freeze/thaw cycles. |
| Long Term Storage |
-20°C |
| Shipping |
Ambient Temperature |
| Regulatory Status |
RUO – Research Use Only |
|---|
- High-throughput screening identifies a novel small-molecule modulator of Hsp70 that selectively enhances ubiquitination and degradation of misfolded neuronal NO synthase: Garcia, A. M., Davis, A. K., et al.; Mol. Pharmacol. 107, 100008 (2025), Abstract
- Activity-dependent tau cleavage by caspase-3 promotes neuronal dysfunction and synaptotoxicity: Opland, C. K., Bryan, M. R., et al.; iScience 26, 106905 (2023), Abstract
- Regional and age-dependent changes in ubiquitination in cellular and mouse models of spinocerebellar ataxia type 3: H. Luo, et al.; Front. Mol. Neurosci. 16, 1154203 (2023), Abstract
- Lucanthone, Autophagy Inhibitor, Enhances the Apoptotic Effects of TRAIL through miR-216a-5p-Mediated DR5 Upregulation and DUB3-Mediated Mcl-1 Downregulation: J.Y. Yoon, et al.; Int. J. Mol. Sci. 23, 17 (2022), Abstract
- Chaperone-mediated autophagy regulates adipocyte differentiation: S. Kaushik, et al.; Sci. Adv. 8, eabq2733 (2022), Abstract
- EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production: J. Nowakowska-Gołacka, et al.; Int. J. Mol. Sci. 23, 117 (2022), Abstract
- KPNB1 modulates the Machado–Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP: M. Abeditashi, et al.; Cell. Mol. Life Sci. 79, 401 (2022), Abstract
- Supplementation with uric and ascorbic acid protects stored red blood cells through enhancement of non-enzymatic antioxidant activity and metabolic rewiring: V.L. Tzounakas, et al.; Redox Biol. 57, 102477 (2022), Abstract
- Red Blood Cell Proteasome in Beta-Thalassemia Trait: Topology of Activity and Networking in Blood Bank Conditions: A.T. Anastasiadi, et al.; Membranes 11, 716 (2021), Abstract
- Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice: Korovila, I., Höhn, A., et al.; Antioxidants (Basel) 10, (2021), Abstract
- Mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC: Liu, Y. T., Sliter, D. A., et al.; Autophagy 17, 3753 (2021), Abstract
- HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue: Hauffe, R., Rath, M., et al.; Mol. Metab. 53, 101276 (2021), Abstract
- Males and Females Differ in the Subcellular and Brain Region Dependent Regulation of Proteasome Activity by CaMKII and Protein Kinase A: R.K. Devulapalli, et al.; Neuroscience 418, 1 (2019), Abstract
- Shifting the balance of autophagy and proteasome activation reduces proteotoxic cell death: a novel therapeutic approach for restoring photoreceptor homeostasis: Qiu, Y., Yao, J., et al.; Cell Death Dis. 10, 547 (2019), Abstract
- An influenza virus-triggered SUMO switch orchestrates co-opted endogenous retroviruses to stimulate host antiviral immunity: Schmidt, N., Domingues, P., et al.; PNAS 116, 17399 (2019), Abstract
- Inhibiting autophagy reduces retinal degeneration caused by protein misfolding: Yao, J., Qiu, Y., et al.; Autophagy 14, 1226 (2018), Abstract
- Functional analysis of Brassica napus phloem protein and ribonucleoprotein complexes: A. Ostendorp, et al.; New Phytol. 214, 1188 (2017), Application(s): Proteasome inhibition in phloem sap, Abstract — Full Text
- A leptospiral AAA+ chaperone-Ntn peptidase complex, HslUV, contributes to the intracellular survival of Leptospira interrogans in hosts and the transmission of leptospirosis: S.L. Dong, et al.; Emerg. Microbes Infect. 6, e105 (2017), Abstract — Full Text
- 18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer’s Disease Progression in Caenorhabditis elegans and Neuronal Cultures: Papaevgeniou, N., Sakellari, M., et al.; Antioxid. Redox Signal. 25, 855 (2016), Abstract
- AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA: Kaushik, S., Cuervo, A. M., et al.; Autophagy 12, 432 (2016), Abstract
- The Molecular Chaperone Hsp70 Promotes the Proteolytic Removal of Oxidatively Damaged Proteins by the Proteasome: S. Reeg, et al.; Free Radic. Biol. Med. 99, 153 (2016), Application(s): Immunoblot Analysis, Abstract
- Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex: S. Ding, et al.; PLoS Pathology 12, e1005929 (2016), Application(s): Cell treatment for immunoprecipitation, Abstract — Full Text
- Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity: A. Rodríguez-García, et al.; Gene Ther. 22, 596 (2015), Application(s): Cell Injection, Abstract
- Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells: K. Husmann, et al.; Biochem. Biophys. Res. Commun. 464, 1222 (2015), Application(s): Cell Culture, Abstract
- Pharmacogenetic stimulation of cholinergic pedunculopontine neurons reverses motor deficits in a rat model of Parkinson’s disease: I.S. Pienaar, et al.; Mol. Neurodegener. 10, 47 (2015), Application(s): Cell Culture, Abstract — Full Text
- Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson’s is associated with histone acetylation and up-regulation of neurotrophic factors: I.F. Harrison, et al.; Br. J. Pharmacol. 172, 4200 (2015), Application(s): Cell Culture, Abstract
- Associated Degeneration of Ventral Tegmental Area Dopaminergic Neurons in the Rat Nigrostriatal Lactacystin Model of Parkinsonism and their Neuroprotection by Valproate: I.F. Harrison, et al.; Neurosci. Lett. 614, 16 (2015), Application(s): Stereotaxic lesioning of the SNpc, Abstract
- Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity: Haller, M., Hock, A. K., et al.; Autophagy 10, 2269 (2015), Abstract
- Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-κB Activity: P.F. Lindholm, et al.; J. Clin. Cell. Immunol. 6, 308 (2015), Application(s): Cell Culture, Abstract — Full Text
- Protein kinase LKB1 promotes RAB7-mediated neuropilin-1 degradation to inhibit angiogenesis: Okon, I. S., Coughlan, K. A., et al.; J. Clin. Invest. 124, 4590 (2014), Abstract
- Assessment of Cytokine-Modulated Proteasome Activity: C.J. Kirk, et al.; Methods Mol. Biol. 1172, 147 (2014), Abstract
- Cyclin C is a haploinsufficient tumour suppressor: Li, N., Fassl, A., et al.; Nat. Cell Biol. 16, 1080 (2014), Abstract
- Protochlamydia induces apoptosis of human HEp-2 cells through mitochondrial dysfunction mediated by chlamydial protease-like activity factor: Matsuo, J., Nakamura, S., et al.; PLoS One 8, e56005 (2013), Abstract
- CDK6 binds and promotes the degradation of the EYA2 protein: Kohrt, D., Crary, J., et al.; Cell Cycle 13, 62 (2013), Abstract
- Mast Cell Subsets and Their Functional Modulation by the Acanthocheilonema viteae Product ES-62: D.H. Ball, et al.; J. Parasitol. Res. 2013, 961268 (2013), Abstract — Full Text
- Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28: M. Hernebring, et al.; Sci. Rep. 3, 1381 (2013), Abstract — Full Text
- Cys-27 variant of human δ-opioid receptor modulates maturation and cell surface delivery of Phe-27 variant via heteromerization: T.T. Leskelä, et al.; J. Biol. Chem. 287, 5008 (2012), Abstract — Full Text
- Protein carbonylation and aggregation precede neuronal apoptosis induced by partial glutathione depletion: A. Dasgupta, et al.; ASN Neuro 4, e00084 (2012), Abstract — Full Text
- Novel Cell- and Tissue-Based Assays for Detecting Misfolded and Aggregated Protein Accumulation Within Aggresomes and Inclusion Bodies: D. Shen, et al.; Cell Biochem. Biophys. 60, 173 (2011), Abstract — Full Text
- Cell surface rescue of kidney anion exchanger 1 mutants by disruption of chaperone interactions: S.T. Patterson, et al.; J. Biol. Chem. 285, 33423 (2010), Abstract — Full Text
- Secretion stimulates intramembrane proteolysis of a secretory granule membrane enzyme: Rajagopal, C., Stone, K. L., et al.; J. Biol. Chem. 285, 34632 (2010), Abstract
- Role of high-mobility group box 1 protein and poly(ADP-ribose) polymerase 1 degradation in Chlamydia trachomatis-induced cytopathicity: Yu, H., Schwarzer, K., et al.; Infect. Immun. 78, 3288 (2010), Abstract
- HDAC-class II specific inhibition involves HDAC proteasome-dependent degradation mediated by RANBP2: Scognamiglio, A., Nebbioso, A., et al.; Biochim. Biophys. Acta 1783, 2030 (2008), Abstract
- Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: a microarray analysis: E.H. Yew et al.; J. Neurochem. 94, 943 (2005), Abstract
- Effect of geldanamycin on androgen receptor function and stability: Vanaja, D. K., Mitchell, S. H., et al.; Cell Stress Chaperones 7, 55 (2002), Abstract
- Lactacystin inhibits cathepsin A activity in melanoma cell lines: L. Kozlowski, et al.; Tumour Biol. 22, 211 (2001), Abstract
- Lactacystin, a proteasome inhibitor: discovery and its application in cell biology: H.Tomoda & S. Omura; Yakugaku Zasshi 120, 935 (2000), Abstract
- Lactacystin, a specific inhibitor of the proteasome, induces apoptosis and activates caspase-3 in cultured cerebellar granule cells: L.A. Pasquini, et al.; J. Neurosci. Res. 59, 601 (2000), Abstract
- Proteasome inhibitors induce cytochrome c-caspase-3-like protease-mediated apoptosis in cultured cortical neurons: J.H. Qiu, et al.; J. Neurosci. 20, 259 (2000), Abstract
- Lactacystin activates FLICE (caspase 8) protease and induces apoptosis in Fas-resistant adult T-cell leukemia cell lines: Y. Yamada, et al.; Eur. J. Haematol. 64, 315 (2000), Abstract
- Separation of cathepsin A-like enzyme and the proteasome: evidence that lactacystin/beta-lactone is not a specific inhibitor of the proteasome: H. Ostrowska, et al.; Int. J. Biochem. Cell. Bio. 32, 747 (2000), Abstract
- Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression: D. Kim, et al.; Biochem. Biophys. Res. Commun. 254, 264 (1999), Abstract
- Proteasome inhibitors induce mitochondria-independent apoptosis in human glioma cells: H. Kitagawa, et al.; FEBS Lett. 443, 181 (1999), Abstract
- The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo- and radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha-initiated apoptosis: J. Delic, et al.; Br. J. Cancer 77, 1103 (1998), Abstract
- Lactacystin, proteasome function, and cell fate: G. Fenteany & S.L. Schreiber; J. Biol. Chem. 273, 8545 (1998), Abstract
- The role of proteolysis during differentiation of Trypanosoma brucei from the bloodstream to the procyclic form: M.C. Mutomba & C.C. Wang; Mol. Biochem. Parasitol. 93, 11 (1998), Abstract
- Proteasome inhibitors prevent the degradation of familial Alzheimer’s disease-linked presenilin 1 and potentiate A beta 42 recovery from human cells: P. Marambaud, et al.; Mol. Med. 4, 147 (1998), Abstract
- Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation: A. Craiu, et al.; J. Biol. Chem. 272, 56 (1997), Abstract
- Degradation of 3-hydroxy-3-methylglutaryl-CoA reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis: T.P. McGee, et al.; J. Biol. Chem. 271, 25630 (1996), Abstract
- Novel inhibitors of the proteasome and their therapeutic use in inflammation: J. Adams & R. Stein; Annual Rep. Med. Chem. 31, 279 (1996)
- Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway: H. Yoshida, et al.; Cancer Res. 56, 2945 (1996), Abstract
- Proteasome pathway operates for the degradation of ornithine decarboxylase in intact cells: Y. Murakami, et al.; Biochem. J. 317, 77 (1996), Abstract
- Degradation of a mutant secretory protein, alpha1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity: D. Qu, et al.; J Biol Chem 271, 22791 (1996), Abstract
- Lactacystin, an inhibitor of the proteasome, blocks the degradation of a mutant precursor of glycosylphosphatidylinositol-linked protein in a pre-Golgi compartment: K. Oda, et al.; Biochem. Biophys. Res. Commun. 219, 800 (1996), Abstract
- Proteasome-dependent regulation of p21WAF1/CIP1 expression: M.V. Blagosklonny, et al.; Biochem. Biophys. Res. Commun. 227, 564 (1996), Abstract
- Lactacystin increases LDL receptor level on HepG2 cells: H. Miura, et al.; Biochem. Biophys. Res. Commun. 227, 684 (1996), Abstract
- Enhancement of CPP32-like activity in the TNF-treated U937 cells by the proteasome inhibitors: E. Fujita, et al.; Biochem. Biophys. Res. Commun. 224, 74 (1996), Abstract
- The neuritogenesis inducer lactacystin arrests cell cycle at both G0/G1 and G2 phases in neuro 2a cells: M. Katagiri, et al.; J. Antibiot. (Tokyo) 48, 344 (1995), Abstract
- Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human monoblast U937 cells: S. Imajoh-Ohmi, et al.; Biochem. Biophys. Res. Commun. 217, 1070 (1995), Abstract
- Degradation process of ligand-stimulated platelet-derived growth factor beta-receptor involves ubiquitin-proteasome proteolytic pathway: S. Mori, et al.; J. Biol. Chem. 270, 29447 (1995), Abstract
- Structure-activity relationships of lactacystin, the first non-protein neurotrophic factor: T. Nagamitsu et al.; J Antibiot (Tokyo) 48, 747 (1995), Abstract
- Neuronal differentiation of Neuro 2a cells by lactacystin and its partial inhibition by the protein phosphatase inhibitors calyculin A and okadaic acid: H. Tanaka et al.; Biochem. Biophys. Res. Commun. 216, 291 (1995), Abstract
- Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin: G. Fenteany, et al.; Science 268, 726 (1995), Abstract
- A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line: G. Fenteany, et al.; PNAS 91, 3358 (1994), Abstract
- Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al.; J. Antibiot. (Tokyo) 44, 113 (1991), Abstract
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