Eeyarestatin I

Terminally misfolded proteins, recognized by chaperones on the endoplasmic reticulum (ER), are transported to depots for ubiquitination and proteasomal degradation by the ER-associated protein degradation (ERAD) pathway. Eeyarestatin 1 is an inhibitor of the ERAD pathway, blocking the degradation of misfolded proteins at a dose of 8 µM.[1] It associates with the p97-associated deubiquitinating complex in cells, preventing deubiquitination of substrates by ataxin-3.[2],[3] Eeyarestatin 1, at 4 µM, interferes with both retrograde and anterograde trafficking of proteins, including certain toxins, and potentially, viruses.[4]
终端错折蛋白质被内质网上分子伴侣识别后，通过内质网相关蛋白质降解途径（ERAD）被转运到质体进行泛素化和蛋白酶体降解。Eeyarestatin 1是一种ERAD通路的抑制剂，能够以8µM的剂量阻止错折蛋白的降解[1]。它与p97相关联的去泛素化复合物结合于细胞中，阻止ataxin-3对底物的去泛素化[2],[3]。在4µM的剂量下，Eeyarestatin 1干扰蛋白质的逆行和顺行运输，包括某些毒素和可能的病毒[4]。

Reference:
[1]. Fiebiger, E., Hirsch, C., Vyas, J.M., et al. Dissection of the dislocation pathway for type I membrane proteins with a new small molecule inhibitor, eeyarestatin. Molecular Biology of the Cell 15, 1635-1646 (2004).
[2]. Wang, Q., Li, L., and Ye, Y. Inhibition of p97-dependent protein degradation by Eeyarestatin I. The Journal of Biological Chemisty 283(12), 7445-7454 (2008).
[3]. Wang, Q., Shinkre, B.A., Lee, J.G., et al. The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group. PLoS One 5(11), 1-12 (2010).
[4]. Aletrari, M.O., McKibbin, C., Williams, H., et al. Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways. PLoS One 6(7), 1-11 (2011).