Reactivos e instrumentos para inmunología, biología celular y biología molecular.

Epoxomicin [134381-21-8]

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Referencia HY-13821-5mg

embalaje : 5mg

Marca : MedChemExpress

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Descripciòn

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^[1]^[2]^[3]^[4]^[5].

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.

Peso molecular

554.72

Fòrmula

C₂₈H₅₀N₄O₇

No. CAS

134381-21-8

Appearance

Solid

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

Structure Classification

Ketones, Aldehydes, Acids

Initial Source

Microorganisms

actinomycete strain NumberQ996-17

Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

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

Solvente y solubilidad

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)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* 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.

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

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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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.

Pureza y Documentación

Purity: 99.60%

Ficha de datos (282 KB) SDS (252 KB)

COA (254 KB) RP-HPLC (264 KB) MS (228 KB)

Instrucciones de manejo (2659 KB)

Referencias

[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]

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Referencia

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Precio Sin IVA

M2193-5mg

Epoxomicin [134381-21-8]

5mg

Epoxomicin [134381-21-8]

Referencia HY-13821-5mg

Marca : MedChemExpress

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