Epoxomicin
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.
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 554.7 |
| Cas No. | 134381-21-8 |
| Formula | C28H50N4O7 |
| Synonyms | Epoxomicin, BU4061T, BU-4061T |
| Solubility | ≥27.73 mg/mL in DMSO; insoluble in H2O; ≥77.4 mg/mL in EtOH |
| 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 |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
HEK293T cells |
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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. |
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Reaction Conditions |
Incubated at 0.2 μM or 2 μM epoxomicin for 1 hour |
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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] | |
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Animal models |
C57BL6 |
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Dosage form |
Epoxomicin (0.58 mg/kg) solubilized in 10% DMSO/PBS were injected i.p. daily for 6 days? |
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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 h postchallenge. |
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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. |
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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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| Description | Epoxomicin is a selective and irreversible inhibitor of 20S proteasome with an IC50 value of 4 nM. | |||||
| Targets | 20S proteasome | |||||
| IC50 | 4 nM | |||||
Quality Control & MSDS
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