Epoxomicin

Biological Activity

Epoxomicin (BU 4061T) is a naturally occurring selective proteasome inhibitor with anti-inflammatory activity. Epoxomicin covalently binds to the LMP7, X, MECL1, and Z catalytic subunits of the proteasome. Epoxomicin (BU 4061T) 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. Epoxomicin also effectively inhibits NF-kappaB activation in vitro and potently blocks in vivo inflammation in the murine ear edema assay. In contrast to peptide aldehyde proteasome inhibitors, epoxomicin does not inhibit nonproteasomal proteases such trypsin, chymotrypsin, papain, calpain, and cathepsin B at concentrations of up to 50 microM. Treatment of proliferating cells with epoxomicin results in cell death through accumulation of ubiquinated proteins.

Product Citations

• 

  Arch Virol. 2021 Aug;166(8):2173-2185.

  Interplay of the ubiquitin proteasome system and the innate immune response is essential for the replication of infectious bronchitis virus
  Epoxomicin purchased from AbMole

• 

  Mol Cell. 2020 Nov 19;80(4):607-620.e12.

  Paradoxical Mitophagy Regulation by PINK1 and TUFm
  Epoxomicin purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Mol Cell (2020), Figure 4, Epoxomicin (Abmole Bioscience Inc.)
	Method	Cell Culture
	Cell Lines	HeLa and HEK293T cell lines
	Concentrations	100 µM
	Incubation Time	2-12 hours
	Results	CCCP treatment induced accumulation of mitochondrion-localized fulllength PINK1 protein and an enhanced p-S222-TUFm signal;applying the proteasome inhibitor MG132 or epoxomicin elevated cytosolic and mitochondrial cleaved PINK1 and the p-S222-TUFm signal, and so did the autophagosome formation inhibitors CK636 and Baf-A1, but to a lesser extent

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Aboulaila M, et al. Vet Parasitol. Evaluation of the in vitro growth-inhibitory effect of epoxomicin on Babesia parasites.

[2] Czesny B, et al. Antimicrob Agents Chemother. The proteasome inhibitor epoxomicin has potent Plasmodium falciparum gametocytocidal activity.

[3] Schwarz K, et al. J Immunol. The selective proteasome inhibitors lactacystin and epoxomicin can be used to either up- or down-regulate antigen presentation at nontoxic doses.

[4] Meng L, et al. Proc Natl Acad Sci U S A. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity.