Eeyarestatin I

Biological Activity

Eeyarestatin I is a potent inhibitor of endoplasmic reticulum associated protein degradation (ERAD). Specifically targets the p97-associated deubiquitinating process (PAD) and inhibits ataxin-3 (atx3)-dependent deubiquitination. Also inhibits Sec61-mediated protein translocation at the ER. Displays cytotoxic activity preferentially against cancer cells; induces cell death via the proapoptotic protein NOXA. Also enhances adeno-associated viral transduction in multiple cells types.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

1. Enhanced endoplasmic reticulum entry of tumor antigen is crucial for cross-presentation induced by dendritic cell-targeted vaccination.
   Wang, Hongxia, Yu, Xiaofei, Guo, Chunqing, Zuo, Daming, Fisher, Paul B, Subjeck, John R, Wang, Xiang-Ya
   J Immunol, 2013;191(12):6010-21.
2. Caveosomal oxidative stress causes Src-p21ras activation and lysine 63 TRAF6 protein polyubiquitination in iron-induced M1 hepatic macrophage activation.
   Zhong S, Xu J, Li P, Tsukamoto H
   J Biol Chem, 2102;287(38):32078-84.
3. Combining valosin-containing protein (VCP) inhibition and suberanilohydroxamic acid (SAHA) treatment additively enhances the folding, trafficking, and function of epilepsy-associated gamma-aminobutyric acid, type A (GABAA) receptors.
   Han D, Di X, Fu Y, Mu T
   J Biol Chem, 2015;290(1):325-37.
4. Grp94 Protein Delivers ?-Aminobutyric Acid Type A (GABAA) Receptors to Hrd1 Protein-mediated Endoplasmic Reticulum-associated Degradation
   XJ Di, YJ Wang, DY Han, YL Fu, AS Duerfeldt, BS Blagg, TW Mu
   J. Biol. Chem., 2016;291(18):9526-39.
5. Inhibition of p97-dependent protein degradation by eeyarestatin I.
   Wang et al.
   J.Biol.Chem., 2008;283:7445
6. Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways.
   Aletrari et al.
   PLoS One, 2011;6:e22713
7. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells.
   Wang et al.
   Proc.Natl.Acad.Sci.USA, 2008;106:2200
8. Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum.
   Cross et al.
   J.Cell Science, 2009;122:4393
9. Chemical modulation of endocytic sorting augments adeno-associated viral transduction.
   Berry and Asokan et al.
   J.Biol.Chem., 2016;291:939

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