Epoxomicin | Irreversible 20S proteasome inhibitor

Epoxomicin (134381-21-8) is a potent, selective and cell permeable irreversible inhibitor of the 20S proteasome.¹ It does not inhibit non-proteasomal proteases such as papain, chymotrypsin, trypsin, calpain and cathepsin B at concentrations up to 50 μM.¹ Epoxomicin was isolated from Actinomycete strain Q996-17 and displayed in vivo antitumor activity against B16 melanoma cells.² Epoxomicin caused a progressive model of Parkinson’s disease in various systems.^3,4,5 This model has been disputed.^6,7

References/Citations:

1) Meng et al. (1999), Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo anti-inflammatory activity; Proc. Natl. Acad. Sci. USA, 96 10403
2) Hanada et al. (1992), Epoxomicin, a new antitumor agent of microbial origin; J. Antibiot. (Tokyo), 45 1746
3) McNaught et al. (2004), Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease; Ann. Neurol., 56 149
4) Matsui et al. (2010), Proteasome inhibition in medaka brain induces the features of Parkinson’s disease; J. Neurochem., 115 178
5) Metcalfe et al. (2012), Coordination between proteasome impairment and caspase activation leading to TAU pathology:neuroprotection by cAMP; Cell Death Diff., 3 e326
6) Kordower et al. (2006), Failure of proteasome inhibitor administration to provide a model of Parkinson’s disease in rats and monkeys; Ann. Neurol., 60 264
7) Bove et al. (2006), Proteasome inhibition and Parkinson’s disease modeling; Ann. Neurol., 60 260