Epoxomicin

Epoxomicin is a potent anti-tumor agent isolated from Actinomycetes that is used as a selective and irreversible inhibitor of the 20S proteasome. It inhibits proteasome activity in cell growth assays with an IC50 value of 4 nM and demonstrates potent cytotoxicity against B16-F10, HCT116, and Moser solid tumor cells, as well as P388 and K562 leukemia cells with IC50 values ranging from 2-44 nM. By inhibiting osteoblast proteasome activity, epoxomicin stimulates bone formation at concentrations as low as 10 nM. Intraperitoneal injection of 1.5 mg/kg epoxomicin given daily for two weeks induces Parkinson's-like symptoms in rats and addition of 100 nM epoxomicin to rat ventral midbrain cultures results in apoptosis specific to dopaminergic neurons. Epoxomicin-induced parkinsonism can be a useful model to examine mechanisms and therapies for the disease.Formal Name: N-acetyl-N-methyl-L-isoleucyl-L-isoleucyl-N-[(1S)-3-methyl-1-[[(2R)-2-methyloxiranyl]carbonyl]butyl]-L-threoninamide. CAS Number: 134381-21-8. Synonyms: BU 4061T. Molecular Formula: C28H50N4O7. Formula Weight: 554.7. Purity: >98%. Formulation: (Request formulation change), A solution in DMSO. Solubility: DMSO: 10 mg/ml. SMILES: CC[C@H](C)[C@@H](NC(=O)[C@H]([C@@H](C)CC)N(C)C(=O)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](CC(C)C)C(=O)[C@]1(C)OC1. InChi Code: 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. InChi Key: DOGIDQKFVLKMLQ-JTHVHQAWSA-N.