For research use only. Not for therapeutic Use.
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].
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].
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].
| Catalog Number | I001311 |
| CAS Number | 134381-21-8 |
| Synonyms | (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 |
| Molecular Formula | C28H50N4O7 |
| Purity | ≥95% |
| InChI | 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 |
| InChIKey | DOGIDQKFVLKMLQ-JTHVHQAWSA-N |
| 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 |
| Reference | [1]. Hanada M, et al. Epoxomicin, a new antitumor agent of microbial origin. J Antibiot (Tokyo). 1992 Nov;45(11):1746-52. [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. [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. [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. [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. |
