| Size | Price | Stock | Qty |
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| 500μg |
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| 1mg |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Epoxomicin (formerly also known as BU-4061T) is a novel, potent, selective, cell-permeable, irreversible proteasome inhibitor with anti-inflammatory activity. It inhibits the 20S proteasome's CH-L activity primarily, while also inhibiting the catalytic activities of PGPH and T-L at 100- and 1000-fold reduced rates. Epoxomicin's unique α-epoxy ketone moiety creates covalent bonds with specific catalytic subunit residues, thereby impeding the enzyme's function.
| Targets |
20S proteasome
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|---|---|
| ln Vitro |
Epoxomicin exhibits strong cytotoxic effects on every tested cell type. Epoxomicin has been shown to inhibit the growth of B16-F10, HCT116, Moser, P388, and K562 cells, with IC50 values of 0.002 μg/mL, 0.005 μg/mL, 0.044 μg/mL, 0.002 μg/mL, and 0.037 μg/mL[1].
Epoxomicin possesses antiproliferative activity against EL4 lymphoma cells, with an IC50 of 4 nM[2]. |
| ln Vivo |
Epoxomicin (0.063-1 mg/kg; intraperitoneal injection; once daily; for 9 days; male BDFX mice) treatment has a strong antitumor effect, with a minimum dosage of 0.13 mg/kg/day being effective[1].
Epoxomicin also potently blocks in vivo inflammation in the murine ear edema assay and effectively inhibits NF-κB activation in vitro[3]. Epoxomicin is given intraperitoneally over a two-week period to adult rats. The animals showed signs of progressive Parkinsonism, including bradykinesia, rigidity, tremor, and abnormal posture, after a latency of one to two weeks. Postmortem examinations reveal dopaminergic cell death with apoptosis and striatal dopamine depletion in the substantia nigra pars compacta[4]. |
| Enzyme Assay |
In assay solutions for proteasome inhibition assays, peptide-AMC substrates (5 μM Suc-LLVY-AMC, 5 μM Z-LLE-AMC, and 5 μM Boc-LRR-AMC) and epopoximin in DMSO are added at a final DMSO concentration of 1%. The assay buffer that is utilized is as follows: pH 8.0/0.5 mM EDTA with 20 mM Tris-HCl (plus 0.035% SDS for Z-LLE-AMC and Suc-LLVY-AMC assays). After adding the bovine red blood cell proteasome to the assay buffer containing substrates and doxomicin at a final volume of 100 μL at room temperature (23 °C), the fluorescence emission is immediately measured at 460 nm (λex, 360 nM) using a Cytofluor fluorescence plate reader for 50 minutes.
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| Cell Assay |
After a pretreatment of vehicle, losartan (10μM), epoxomicin (10μM), or vehicle control, LECs were treated for a full day with either saline or Ang II (100μM).
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| Animal Protocol |
BALB/c mice
2.9 mg/kg intraperitoneal injection |
| References | |
| Additional Infomation |
Epoxomicin is a tripeptide consisting of an Ile-Ile-Thr-NH2 sequence N-substituted on the threonamide amidic nitrogen with a (2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl group and with acetyl and methyl groups on the nitrogen of the isoleucine residue distal to the threonamide; a naturally occurring selective proteasome inhibitor with anti-inflammatory activity. It has a role as a proteasome inhibitor. It is a member of morpholines and a tripeptide.
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| Molecular Formula |
C28H50N4O7
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| Molecular Weight |
554.72
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| Exact Mass |
554.367
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| Elemental Analysis |
C, 60.63; H, 9.09; N, 10.10; O, 20.19
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| CAS # |
134381-21-8
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| Related CAS # |
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| PubChem CID |
11226684
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
795.7±60.0 °C at 760 mmHg
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| Melting Point |
107-109ºC
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| Flash Point |
435.0±32.9 °C
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| Vapour Pressure |
0.0±6.3 mmHg at 25°C
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| Index of Refraction |
1.504
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| LogP |
3.32
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
39
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| Complexity |
895
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| Defined Atom Stereocenter Count |
8
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| SMILES |
O=C([C@@H](NC([C@H]([C@@H](C)O)NC([C@@H](NC([C@H]([C@@H](C)CC)N(C)C(C)=O)=O)[C@@H](C)CC)=O)=O)CC(C)C)[C@@]1(C)CO1
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| InChi Key |
DOGIDQKFVLKMLQ-JTHVHQAWSA-N
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| InChi Code |
InChI=1S/C28H50N4O7/c1-11-16(5)21(30-27(38)23(17(6)12-2)32(10)19(8)34)25(36)31-22(18(7)33)26(37)29-20(13-15(3)4)24(35)28(9)14-39-28/h15-18,20-23,33H,11-14H2,1-10H3,(H,29,37)(H,30,38)(H,31,36)/t16-,17-,18+,20-,21-,22-,23-,28+/m0/s1
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| 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
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8027 mL | 9.0136 mL | 18.0271 mL | |
| 5 mM | 0.3605 mL | 1.8027 mL | 3.6054 mL | |
| 10 mM | 0.1803 mL | 0.9014 mL | 1.8027 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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