Home Proteases Proteasome inhibitor Epoxomicin (BU-4061T)

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Epoxomicin (BU-4061T) Proteasome inhibitor

Cat.No.S7038

Epoxomicin (BU-4061T, Aids010837) is a selective proteasome inhibitor with anti-inflammatory activity, which primarily inhibits the CH-L activity of the 20S proteasome, while T-L and PGPH catalytic activities are also inhibited at 100- and 1000-fold reduced rate. This compound promotes apoptosis and can be used to induce animal models of Parkinson's Disease.
Epoxomicin (BU-4061T) Proteasome inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 554.72

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Quality Control

Batch: S703801 DMSO]100 mg/mL]false]Ethanol]100 mg/mL]false]Water]Insoluble]false Purity: 99.87%
99.87

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PC3 Antiproliferative assay Antiproliferative activity against human PC3 cell line, IC50 = 0.001 μM. 16686537
WM266.4 Cytotoxicity assay 72 hrs Cytotoxicity against human WM266.4 cells after 72 hrs by ATPlite assay, IC50 = 0.0048 μM. 22206869
lymphoblastoid cells Function assay Inhibition of chymotrypsin like 20S proteasome activity in lymphoblastoid cells, IC50 = 0.005 μM. 17996987
LCL Function assay 12 hrs Inhibition of chymotrypsin-like activity of 20S proteasome beta2 in human LCL cells after 12 hrs, IC50 = 0.005 μM. 20687609
DLD1 Function assay 6 hrs Inhibition of chymotrypsin-like activity of 20S proteasome in human DLD1 cells transfected with 4Ub-Luc gene using Succinyl-Leu-Leu-Val-Tyr-AMC as substrate after 6 hrs by spectrofluorometric analysis, IC50 = 0.006 μM. 22206869
HEK293 Function assay 2 hrs Inhibition of chymotrypsin-like activity of proteasome beta-5 subunit in HEK293 cells using Suc-LLVY-Glo as substrate incubated for 2 hrs prior to substrate addition measured after 10 mins by cell-based proteasome-Glo beta5 assay, IC50 = 0.026 μM. 23540790
DLD1 Function assay 6 hrs Inhibition of peptide-glutamyl-peptide-hydrolyzing activity of 20S proteasome in human DLD1 cells transfected with 4Ub-Luc gene using Z-Leu-Leu-Glu-AMC as substrate after 6 hrs by spectrofluorometric analysis, IC50 = 0.06 μM. 22206869
lymphoblastoid cells Function assay Inhibition of trypsin like 20S proteasome activity in lymphoblastoid cells, IC50 = 0.284 μM. 17996987
LCL Function assay 12 hrs Inhibition of trypsin-like activity of 20S proteasome beta2 in human LCL cells after 12 hrs, IC50 = 0.284 μM. 20687609
HEK293 Function assay 2 hrs Inhibition of postacid activity of 20s proteasome beta-1 subunit in HEK293 cells using Z-nLPnLD-Glo as substrate incubated for 2 hrs prior to substrate addition measured after 10 mins by cell-based proteasome-Glo beta1 assay, IC50 = 0.3 μM. 23540790
KB-8-5-11 Function assay P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency = 2.5929 μM. 31515284
lymphoblastoid cells Function assay Inhibition of caspase like 20S proteasome activity in lymphoblastoid cells, IC50 = 4.56 μM. 17996987
LCL Function assay 12 hrs Inhibition of PGPH catalytic activity of 20S proteasome beta2 in human LCL cells after 12 hrs, IC50 = 4.56 μM. 20687609
KB-3-1 Function assay P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen 31515284
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (180.27 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 554.72 Formula

C28H50N4O7

 Storage (From the date of receipt)
CAS No. 134381-21-8 Download SDF Storage of Stock Solutions

Synonyms Aids010837 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

Mechanism of Action

Features
Epoxomicin is a natural product isolated from an Actinomycetes species.
Targets/IC50/Ki
20S proteasome
In vitro

Epoxomicin (BU-4061T) covalently binds to the LMP7, X, MECL1, and Z catalytic subunits of the proteasome. This compound (100 nM) results in a 30-fold increase in the levels of p53 protein, a known target of the proteasome, in HUVECs. It (10 μM) results in the accumulation of ubiquitinated proteins in HeLa cells, inhibits IκBα degradation by 10-fold, and produces a significant dose-dependent reduction in TNF-α-stimulated NF-κB DNA-binding activity in the same cell line.

It inhibits proliferating of EL4 lymphoma cells with biotinylated chimerae with IC50 of 4 nM.

At 1 μM, it leads to a reduction of LCMV GP33 presentation and an enhancement of GP276 presentation.

This compound inhibits growth of Babesia bigemina with IC50 of 4 nM. It (0.5 mg/kg and 0.05 mg/kg) results in peak parasitemia levels of 34.8% and 42.3% in B. microti.

Epoxomicin (100 nM) decreases the total parasitemia by 78%, 86% and 77% in Plasmodium falciparum. At 10 μM, it inhibits gametogenesis and exflagellation as well as development into oocysts of anopheles mosquitoes.

Kinase Assay
Enzyme Kinetic Assays
For proteasome inhibition assays, peptide-AMC substrates (5 μM Suc-LLVY-AMC, 5 μM Z-LLE-AMC, and 5 μM Boc-LRR-AMC) and Epoxomicin (BU-4061T) in DMSO are added to assay solutions at a final DMSO concentration of 1%. The following assay buffer is used: 20 mM Tris⋅HCl, pH 8.0/0.5 mM EDTA (plus 0.035% SDS for Suc-LLVY-AMC and Z-LLE-AMC assays). Bovine red blood cell proteasome is added to the assay buffer containing substrates and this compound at a final volume of 100 μL at room temperature (23℃) in a Dynex Microfluor II 96-well plate and the fluorescence emission immediately is measured at 460 nm (λex, 360 nM) by using a Cytofluor fluorescence plate reader for 50 min.
In vivo

Epoxomicin (BU-4061T) (0.58 mg/kg per day) reduces the CS response by 44% relative to the control group of mice treated with vehicle alone. This compound (2.9 mg/kg) potently inhibits the irritant-associated inflammatory response by 95% when ear edema measurements are made 24 hours postchallenge in mice.

References
  • [4] https://pubmed.ncbi.nlm.nih.gov/19896277/
  • [5] https://pubmed.ncbi.nlm.nih.gov/19651911/

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