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]}.

Proteasome^[1]

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.

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.

554.72

C₂₈H₅₀N₄O₇

134381-21-8

Solid

White to off-white

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

Room temperature in continental US; may vary elsewhere.

* 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.

• [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]