Cat. No.: HY-13821

Epoxomicin

(Synonyms: BU-4061T)

27 Cited Publications

Customer Review

Based on 27 publication(s) in Google Scholar

Epoxomicin (BU-4061T) is an epoxyketone-containing natural product and a potent, selective and irreversible proteasome inhibitor. Epoxomicin covalently binds to the LMP7, X, MECL1, and Z catalytic subunits of the proteasome and potently inhibits primarily the chymotrypsin-like activity. Epoxomicin can cross the blood-brain barrier. Epoxomicin has strongly antitumor and anti-inflammatory activity.

For research use only. We do not sell to patients.

Purity: 99.60%
CAS No.: 134381-21-8
Formula: C₂₈H₅₀N₄O₇
Molecular Weight:554.72

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Epoxomicin Chemical Structure

CAS No.: 134381-21-8

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (27)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

IC₅₀ & Target

Proteasome^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
DLD-1	IC₅₀	0.006 μM Compound: Epoxomicin	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 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	[PMID: 22206869]
DLD-1	IC₅₀	0.06 μM Compound: Epoxomicin	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 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	[PMID: 22206869]
HEK293	IC₅₀	0.026 μM Compound: Epoxomicin	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 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	[PMID: 23540790]
HEK293	IC₅₀	0.3 μM Compound: Epoxomicin	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 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	[PMID: 23540790]
Hepatocyte	IC₅₀	3.95 μM Compound: Epoximicin	Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs	[PMID: 18212104]
Hepatocyte	IC₅₀	3.95 x 10³ nM Compound: Epoximicin	Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs	[PMID: 18212104]
PC-3	IC₅₀	1 nM Compound: 2	Antiproliferative activity against human PC3 cell line Antiproliferative activity against human PC3 cell line	[PMID: 16686537]
RPMI-8226	IC₅₀	0.011 μM Compound: Epoxomicin	Cytotoxicity against human RPMI8226 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay Cytotoxicity against human RPMI8226 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay	[PMID: 30964987]
WM 266-4	IC₅₀	0.0048 μM Compound: Epoxomicin	Cytotoxicity against human WM266.4 cells after 72 hrs by ATPlite assay Cytotoxicity against human WM266.4 cells after 72 hrs by ATPlite assay	[PMID: 22206869]

In Vitro

Epoxomicin shows quite potent cytotoxicities against all of the cells tested. Epoxomicin inhibits the cells growth of B16-F10, HCT116, Moser, P388 and K562 cells of 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 has antiproliferative activity with an IC₅₀ of 4 nM in EL4 lymphoma cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Epoxomicin (0.063-1 mg/kg; intraperitoneal injection; once daily; for 9 days; male BDFX mice) treatment shows significant antitumor effect with the minimumeffective dose of 0.13mg/kg/day^[1].
Epoxomicin also effectively inhibits NF-κB activation in vitro and potently blocks in vivo inflammation in the murine ear edema assay^[3].
Epoxomicin is injected into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive Parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture. Postmortem analyses shows striatal dopamine depletion and dopaminergic cell death with apoptosis in the substantia nigra pars compacta^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male BDFX mice with B16 melanoma^[1]
Dosage:

0.063 mg/kg, 0.13 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg
Administration:

Intraperitoneal injection; once daily; for 9 days
Result:

Exhibited strong therapeutic activity against B16 melanoma.

Chemical Information

CAS No. 134381-21-8
Appearance Solid
Molecular Weight 554.72
Formula C₂₈H₅₀N₄O₇
Color White to off-white
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
Synonyms

BU-4061T
Structure Classification
- Ketones, Aldehydes, Acids
Initial Source
- Microorganisms
actinomycete strain NumberQ996-17
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (27)

All WBIn Vivo Efficacy StudyHistological Imaging/StainingIFRT-PCR

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Journal Impact Factor

Signal Transduct Target Ther

Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses. [Abstract]

2025 Dec 15;10(1):406. PMID: 41392286
Signal Transduct Target Ther

Reprogramming of cancer metabolism via photoresponsive nano-PROTAC enhances pyroptosis-mediated immunotherapy. [Abstract]

2025 Sep 26;10(1):310. PMID: 40998785
Nat Metab

Insulin induces insulin receptor degradation in the liver through EphB4. [Abstract]

2022 Sep;4(9):1202-1213. PMID: 36131205
Cancer Res

Antigen Cross-Presentation by Type-2 Innate Lymphoid Cells Facilitates the Activation of Antitumor CD8+ T Cells. [Abstract]

2025 Apr 17. PMID: 40245114
Nat Commun

Opposing roles of pseudokinases NRBP1 and NRBP2 in regulating L1 retrotransposition. [Abstract]

2025 Jul 11;16(1):6327. PMID: 40645931

Epoxomicin purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Jul 11;16(1):6327. [Abstract]

Epoxomicin treatment (0.1 µM or 0.2 µM, 16 h) did not restore the reduced NRBP1 protein levels resulting from NRBP2 overexpression in HeLa cells.
Nat Commun

20S proteasomes secreted by the malaria parasite promote its growth. [Abstract]

2021 Feb 19;12(1):1172. PMID: 33608523
Adv Sci (Weinh)

OTUD6A in Airway Epithelial Cells Exacerbates Allergic Asthma by Promoting Airway Inflammation and Airway Remodeling Through Deubiquitination of hResistin/mRELMα. [Abstract]

2026 Jan 20:e16355. PMID: 41560298
Redox Biol

MK-886 protects against cardiac ischaemia/reperfusion injury by activating proteasome-Keap1-NRF2 signalling. [Abstract]

2023 Jun:62:102706. PMID: 37098317

Epoxomicin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2023 Jun:62:102706. [Abstract]

Male mice were pretreated with MK-886 (20 mg/kg) and epoxomicin (Epox, 1 mg/kg) at 2 and 24 h before I/R-mediated cardiac injury. Echocardiographic images of the left ventricle (left). Scale bar: 0.2 s. Quantification of EF% and FS% (right, n = 6).

Epoxomicin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2023 Jun:62:102706. [Abstract]

Male mice were pretreated with MK-886 (20 mg/kg) and epoxomicin (Epox, 1 mg/kg) at 2 and 24 h before I/R-mediated cardiac injury. Images of Evans blue and TTC staining (left) for infarct size analysis, with quantification of the infarction area/left ventricular (LV) area and area at risk (AAR)/LV area ratios (right; n = 6).

Epoxomicin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2023 Jun:62:102706. [Abstract]

Male mice were pretreated with MK-886 (20 mg/kg) and epoxomicin (Epox, 1 mg/kg) at 2 and 24 h before I/R-mediated cardiac injury. Images of TUNEL (red), α-actinin (green), and DAPI (blue) staining of cardiac slices (left) and the percentage of TUNEL+ nuclei (right; n = 6).

Epoxomicin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2023 Jun:62:102706. [Abstract]

Male mice were pretreated with MK-886 (20 mg/kg) and epoxomicin (Epox, 1 mg/kg) at 2 and 24 h before I/R-mediated cardiac injury. qPCR analysis of Bax and Bcl-2 mRNA levels in the border zone of the ischemic heart (n = 6) and quantification of the relative Bax/Bcl-2 ratio.

Epoxomicin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2023 Jun:62:102706. [Abstract]

Male mice were pretreated with MK-886 (20 mg/kg) and epoxomicin (Epox, 1 mg/kg) at 2 and 24 h before I/R-mediated cardiac injury. Images of TUNEL (red), α-actinin (green), and DAPI (blue) staining of cardiac slices (left) and the percentage of TUNEL+ nuclei (right; n = 6).
EMBO J

Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system. [Abstract]

2025 Apr 7. PMID: 40195501
Biomed Pharmacother

Proteasome-activating peptide 1 attenuates cardiac ischaemia/reperfusion-induced ferroptosis through the β5i-p53-SLC7A11 axis. [Abstract]

2025 Jun 27:189:118296. PMID: 40580875
Aging Cell

Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets. [Abstract]

2024 Sep 3:e14312. PMID: 39228130
Cell Death Discov

The RNF8/OPTN/KDM6A axis controls macrophage polarization to maintain testicular microenvironment homeostasis. [Abstract]

2025 Jul 24;11(1):339. PMID: 40707433
Cell Death Discov

CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response. [Abstract]

2024 Oct 26;10(1):453. PMID: 39461947
J Med Chem

Development of TSSK1 and TSSK2 Targeted Degraders Reveals Sperm Machinery for Protein Degradation and Potential for Nonhormonal Male Contraception. [Abstract]

2026 Jun 25;69(12):14236-14254. PMID: 42228803
J Med Chem

Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors. [Abstract]

2024 May 9;67(9):7620-7634. PMID: 38634707
Mol Plant Pathol

Phytoplasma effector SWP1 induces witches' broom symptom by destabilizing the TCP transcription factor BRANCHED1. [Abstract]

2018 Dec;19(12):2623-2634. PMID: 30047227

Epoxomicin purchased from MedChemExpress. Usage Cited in: Mol Plant Pathol. 2018 Dec;19(12):2623-2634. [Abstract]

Destabilization of BRC1 mediated by SWP1 is inhibited by proteasome inhibitors Epoxomicin and MG132.
Antimicrob Agents Chemother

Inhibitors of the 20S proteasome β5 subunit as potent and selective agents against Trichomonas vaginalis. [Abstract]

2025 Dec 10;69(12):e0089325. PMID: 41218108
Sci Rep

VPS28 regulates triglyceride synthesis via ubiquitination in bovine mammary epithelial cells. [Abstract]

2024 Dec 28;14(1):31310. PMID: 39732879
RSC Chem Biol

Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells. [Abstract]

2026 Feb 4;7(3):433-443. PMID: 41647277
bioRxiv

Dissecting Complex Interactions Between Ferroptosis and the Proteasome. [Abstract]

2026 Mar 30:2026.03.28.714855. PMID: 41959534
bioRxiv

2024 July 05.
bioRxiv

2024 May 22.
bioRxiv

2024 May 14.
Norwegian University of Science and Technology

2021 Oct.
Norwegian University of Science and Technology

2021 Oct.
Oxid Med Cell Longev

Recombinant High-Mobility Group Box 1 (rHMGB1) Promotes NRF2-Independent Mitochondrial Fusion through CXCR4/PSMB5-Mediated Drp1 Degradation in Endothelial Cells. [Abstract]

2021 Aug 2;2021:9993240. PMID: 34394840
Oxid Med Cell Longev

The Nrf2/PGC1 α Pathway Regulates Antioxidant and Proteasomal Activity to Alter Cisplatin Sensitivity in Ovarian Cancer. [Abstract]

2020 Nov 26;2020:4830418. PMID: 33294122

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (180.27 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (4.51 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (4.51 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (4.51 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Portuguese - PT (252 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Hanada M, et al. Epoxomicin, a new antitumor agent of microbial origin. J Antibiot (Tokyo). 1992 Nov;45(11):1746-52. [Content Brief]

[2]. Kim KB, et al. Proteasome inhibition by the natural products epoxomicin and dihydroeponemycin: insights into specificity and potency. Bioorg Med Chem Lett. 1999 Dec 6;9(23):3335-40. [Content Brief]

[3]. Meng L, 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. [Content Brief]

[4]. McNaught KS, et al. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann Neurol. 2004 Jul;56(1):149-62. [Content Brief]

[5]. Garrett IR, et al. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest. 2003 Jun;111(11):1771-82. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.8027 mL	9.0136 mL	18.0271 mL	45.0678 mL
	5 mM	0.3605 mL	1.8027 mL	3.6054 mL	9.0136 mL
	10 mM	0.1803 mL	0.9014 mL	1.8027 mL	4.5068 mL
	15 mM	0.1202 mL	0.6009 mL	1.2018 mL	3.0045 mL
	20 mM	0.0901 mL	0.4507 mL	0.9014 mL	2.2534 mL
	25 mM	0.0721 mL	0.3605 mL	0.7211 mL	1.8027 mL
	30 mM	0.0601 mL	0.3005 mL	0.6009 mL	1.5023 mL
	40 mM	0.0451 mL	0.2253 mL	0.4507 mL	1.1267 mL
	50 mM	0.0361 mL	0.1803 mL	0.3605 mL	0.9014 mL
	60 mM	0.0300 mL	0.1502 mL	0.3005 mL	0.7511 mL
	80 mM	0.0225 mL	0.1127 mL	0.2253 mL	0.5633 mL
	100 mM	0.0180 mL	0.0901 mL	0.1803 mL	0.4507 mL

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Epoxomicin

MCE Bioactive Compound Library

Natural Product Library Plus

Publications Citing Use of MedChemExpress (MCE) Epoxomicin

Biological Activity

Chemical Information

Publications (27)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Epoxomicin

MCE Bioactive Compound Library

Natural Product Library Plus

Publications Citing Use of MedChemExpress (MCE) Epoxomicin

Biological Activity

Chemical Information

Publications (27)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Epoxomicin Related Classifications

Cat. No.: HY-13821