Eeyarestatin I, a potent endoplasmic reticulum-associated protein degradation (ERAD) inhibitor, is a potent protein translocation inhibitor. It disturbs endoplasmic reticulum (ER) homeostasis and has anticancer activities resembling that of Bortezomib. Eeyarestatin I inhibits Sec61 translocon[1].
Eeyarestatin I (8μM; 1h) modulates protein processing at the ER of cultured mammalian cells, when cells were incubated with 8μM Eeyarestatin I, an almost complete loss of secretory glycoproteins in the media was observed[2]. Eeyarestatin I (0.2-5μM; 4h) abolishes both Zika virus and Usutu virus infectivity in a dose-and time-dependent manner, in agreement with an antiviral activity occurring directly upon the viral particles[3]. Eeyarestatin I (10μM; 24h) abrogates TGF-β1-triggered Klotho reduction in cultured HK-2 cells[4].
Eeyarestatin I (2.5mg/kg; ip, 10d) upregulates renal Klotho protein expression, as well as sKlotho levels , without significantly altering Klotho mRNA level[4]. Inhibition of Valosin-containing protein's function by Eeyarestatin I (50µg/each; sc; 2 times) reduces tumor growth in NSCLC-xenograft model[5].
References:
[1] Cross B C S, McKibbin C, Callan A C, et al. Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum[J]. Journal of cell science, 2009, 122(23): 4393-4400.
[2]. Cross B C S, McKibbin C, Callan A C, et al. Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum[J]. Journal of cell science, 2009, 122(23): 4393-4400.
[3]Rodrigo I, Ballesta C, Nunes E B, et al. Eeyarestatin I, an inhibitor of the valosin-containing protein, exhibits potent virucidal activity against the flaviviruses[J]. Antiviral Research, 2022, 207: 105416.
[4]. Li S S, Kong J W, Yu L X, et al. Abnormally decreased renal Klotho is linked to endoplasmic reticulum-associated degradation in mice[J]. International Journal of Medical Sciences, 2022, 19(2): 321.
[5].Valle C W, Min T, Bodas M, et al. Critical role of VCP/p97 in the pathogenesis and progression of non-small cell lung carcinoma[J]. PloS one, 2011, 6(12): e29073.
Eeyarestatin I是一种有效的内质网相关蛋白降解(ERAD)抑制剂，也是一种有效的蛋白质易位抑制剂。它扰乱内质网 (ER) 稳态，具有与硼替佐米相似的抗癌活性。Eeyarestatin I可抑制Sec61转运蛋白[1]。
Eeyarestatin I（8μM；1h）调节培养的哺乳动物细胞 ER 中的蛋白质加工，当细胞与8μM Eeyarestatin I一起孵育时，培养基中分泌糖蛋白几乎完全消失[2]。Eeyarestatin I（0.2-5μM；4h）以剂量和时间依赖性方式消除寨卡病毒和乌苏图病毒的传染性，这与直接发生在病毒颗粒上的抗病毒活性一致[3]。Eeyarestatin I（10μM；24h）可消除培养的HK-2细胞中TGF-β1引发的Klotho减少[4]。
Eeyarestatin I（2.5 mg/kg；ip；10d）可上调肾脏 Klotho 蛋白表达以及sKlotho水平，而不会显著改变Klotho mRNA水平[4]。Eeyarestatin I （50 µg/each；sc；2次) 抑制含缬氨酸蛋白功能，降低NSCLC异种移植模型中的肿瘤生长[5]。