134381-21-8 Usage
Description
Epoxomicin is a potent, selective, and cell-permeable irreversible inhibitor of the 20S proteasome, a natural product isolated from Actinomyces sp. It is a linear peptide consisting of a threonine or serine residue with α′, β′-epoxyketone derived from leucine or a γ,δ-dehydroleucine. Epoxomicin does not inhibit non-proteasomal proteases such as papain, chymotrypsin, trypsin, calpain, and cathepsin B at concentrations up to 50 μM. It has displayed in vivo antitumor activity against B16 melanoma cells and has been used to study various biological processes.
Uses
Used in Proteasome Biology Studies:
Epoxomicin is used as a research tool in proteasome biology studies to investigate the role of the ubiquitin-proteasome system (UPS) in various cellular processes.
Used in Pheochromocytoma PC12 Cells:
Epoxomicin is used as a ubiquitin-proteasome system (UPS) inhibitor in pheochromocytoma PC12 cells to study the effects of proteasome inhibition on these cells.
Used in Mammary Epithelial MCF-10A Cells:
Epoxomicin is used as a proteasome inhibitor in mammary epithelial MCF-10A cells to investigate the role of proteasome activity in the functioning of these cells.
Used in Chymotryptic Assay in Cardiomyocytes:
Epoxomicin is used as a proteasome inhibitor in a chymotryptic assay in cardiomyocytes to study the effects of proteasome inhibition on heart muscle cells.
Used in Parkinson's Disease Research:
Epoxomicin has been used to cause a progressive model of Parkinson's disease in various systems, although this model has been disputed. It aids in understanding the molecular mechanisms underlying the disease and the potential therapeutic targets.
Biochem/physiol Actions
Epoxomicin binds covalently to the catalytic subunits of proteasome. It forms an adduct with target proteins. It inhibits chymotrypsin-like activity of the proteasome. Epoxomicin also inhibits the nuclear factor κ light chain enhancer of activated B cells (NF-κB) mediated proinflammatory signalling pathway. It is also a potent antitumor and anti-inflammatory agent.
References
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
Check Digit Verification of cas no
The CAS Registry Mumber 134381-21-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,4,3,8 and 1 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 134381-21:
(8*1)+(7*3)+(6*4)+(5*3)+(4*8)+(3*1)+(2*2)+(1*1)=108
108 % 10 = 8
So 134381-21-8 is a valid CAS Registry Number.
InChI:InChI=1/C28H50N4O7/c1-11-16(5)21(30-27(38)23(17(6)12-2)32(10)19(8)34)25(36)31-26(37)22(18(7)33)29-20(13-15(3)4)24(35)28(9)14-39-28/h15-18,20-23,29,33H,11-14H2,1-10H3,(H,30,38)(H,31,36,37)/t16-,17-,18+,20?,21-,22-,23-,28+/m0/s1
