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EpoxomicinProteasome inhibitor

Epoxomicin

Catalog No. A2606
Size Price Stock Qty
10mM (in 1mL DMSO) $500.00 In stock
Evaluation Sample $28.00 In stock
1mg $135.00 In stock
5mg $400.00 In stock
20mg $1,200.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Product Citations

1.Schrader J, Henneberg F, et al. "The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design." Science. 2016 Aug 5;353(6299):594-8. PMID:27493187
2. Khattar, Vinayak, and Jaideep V. Thottassery. "Cks1 proteasomal turnover is a predominant mode of regulation in breast cancer cells: Role of key tyrosines and lysines." International journal of oncology 46.1 (2015): 395-406. PMID:25353373
3.Khattar, Vinayak, et al. "Cks1 proteasomal degradation is induced by inhibiting Hsp90-mediated chaperoning in cancer cells." Cancer chemotherapy and pharmacology (2014): 1-10. PMID:25544127
4.Downey, Sondra L., et al. "Use of Proteasome Inhibitors." Current Protocols in Immunology (2015): 9-10.
5.Tang, Pei-Ciao, and Glen M. Watson. "Proteomic identification of hair cell repair proteins in the model sea anemone Nematostella vectensis." Hearing research (2015). PMID:26183436
6.Welk V, Coux O, Kleene V, Abeza C, Truembach D, Eickelberg O, Meiners S. "Inhibition of Proteasome Activity Induces Formation of Alternative Proteasome Complexes." J Biol Chem. 2016 Apr 18. PMID:27129254

Quality Control

Chemical structure

Epoxomicin

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin
HeLa cells were untreated (-) or treated with 10 μm Epoxomicin (+) as indicated, 4 h later the cells were harvested and the lysates were subjected to immunoblot analysis with anti-ubiquitin or anti-p53 antibodies.

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin

Related Biological Data

Epoxomicin

Biological Activity

Description Epoxomicin is a selective and irreversible inhibitor of 20S proteasome with an IC50 value of 4 nM.
Targets 20S proteasome          
IC50 4 nM          

Protocol

Cell experiment:[1]

Cell lines

HEK293T cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

Incubated at 0.2 μM or 2 μM epoxomicin for 1 hour

Applications

Peptides were degraded by proteasome from cytosolic, mitochondrial, and nuclear proteins. Epoxomicin is a proteasome inhibitor. It decreased the levels of the majority of intracellular peptides, companying with inhibition of the proteasome beta-2 and beta-5 subunits in HEK293T cells.

Animal experiment:[2]

Animal models

C57BL6

Dosage form

Epoxomicin (0.58 mg/kg) solubilized in 10% DMSO/PBS were injected i.p. daily for 6 days 

Applications

Epoxomicin reduced inflammation in response to picrylchloride. Epoxomicin potently inhibited the irritant-associated inflammatory response by 95% when ear edema measurements were made 24 hr postchallenge.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Fricker LD1, Gelman JS, Castro LM et al. Peptidomic analysis of HEK293T cells: effect of the proteasome inhibitor epoxomicin on intracellular peptides. J Proteome Res. 2012 Mar 2;11(3):1981-90.

2. Meng L1, Mohan R, Kwok BH et al. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10403-8.

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Chemical Properties

Cas No. 134381-21-8 SDF Download SDF
Synonyms Epoxomicin,BU4061T,BU-4061T
Chemical Name (2S,3S)-2-[[(2S,3S)-2-[acetyl(methyl)amino]-3-methylpentanoyl]amino]-N-[(2S,3R)-3-hydroxy-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxobutan-2-yl]-3-methylpentanamide
Canonical SMILES CCC(C)C(C(=O)NC(C(C)O)C(=O)NC(CC(C)C)C(=O)C1(CO1)C)NC(=O)C(C(C)CC)N(C)C(=O)C
Formula C28H50N4O7 M.Wt 554.7
Solubility >27.7mg/mL in DMSO Storage Store at -20°C
General tips No
Shipping Condition No

Research Update

1. From epoxomicin to carfilzomib: chemistry, biology, and medical outcomes. Nat Prod Rep. 2013 May;30(5):600-4. doi: 10.1039/c3np20126k.
Abstract
Although it’s a microbial antitumor natural product deemed unfit for clinical development, epoxomicin was turned into YU-101 leading to the discovery of carfilzomin.
2. Peptidomic analysis of HEK293T cells: effect of the proteasome inhibitor epoxomicin on intracellular peptides. J Proteome Res. 2012 Mar 2;11(3):1981-90. doi: 10.1021/pr2012076. Epub 2012 Feb 16.
Abstract
Epoxomicin at 0.2 or 2 uM decreased levels of the majority of intracellular peptides in HEK294T cells through inhibition of beta-2 and beta-5 subunits of proteasome. However, degradation of proteasome through beta-1 subunit was enabled at a higher concentration of epoxomocon.
4. Evaluation of the in vitro growth-inhibitory effect of epoxomicin on Babesia parasites. Vet Parasitol. 2010 Jan 20;167(1):19-27. doi: 10.1016/j.vetpar.2009.09.049. Epub 2009 Oct 3.
Abstract
Epoxomicin is an inhibitor of proteasomal subunits that induces cell death through accumulation of ubiquinated proteins. Epoxomicin exhibited potent in vitro and in vivo inhibition against babesiosis alone or in combination with diminazene aceturate.
5. The proteasome inhibitor epoxomicin has potent Plasmodium falciparum gametocytocidal activity. Antimicrob Agents Chemother. 2009 Oct;53(10):4080-5. doi: 10.1128/AAC.00088-09. Epub 2009 Aug 3.
Abstract
Epoxomicin, a proteasome inhibitor, not only exhibited potent antimalarial activity killing malaria parasites without affecting normal cells but also inhibited oocyst production in the mosquito midgut.

Background

Epoxomicin was originally isolated from the culture medium of an Actinomycetes strain based on its in vivo antitumor activity against murine B16 melanoma. Epoxomicin is a naturally occurring selective proteasome inhibitor with anti-inflammatory activity. [1] Epoxomicin primarily inhibits the activity of CTRL (chymotrypsin-like proteasome).

The novel α-epoxy ketone moiety of Epoxomicin forms covalent bonds with residues in particular catalytic subunits of the enzyme, disabling activity. The trypsin-like and peptidyl-glutamyl peptide hydrolyzing behaviors of the proteasome were both inhibited by Epoxomicin as well (at 100 and 1,000-fold slower rates, respectively). The ubiquitin-proteasome pathway heavily regulates bone formation, and Epoxomicin was shown to increase both bone volume and bone formation rates in rodents.

Another study demonstrates that exposure to Epoxomicin and other proteasome inhibitors leads to dopaminergic cell death, producing a model of Parkinson's disease in vivo. Epoxomicin is an inhibitor of 20S Proteasome. [2]

References:
1. Meng, L; Mohan, R; Kwok, BH; Elofsson, M; Sin, N; Crews, CM (1999). "Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity". PNAS 96 (18): 10403–10408.
2. Epoxomicin, Santa Cruz Biotechnology.