Eeyarestatin I (EerI ) is an inhibitor of endoplasmic reticulum-associated degradation (ERAD). It disturbs endoplasmic reticulum (ER) homeostasis and has anticancer activities resembling that of Bortezomib. ESI induced cell death in JEKO-1 cells with an IC50 of 4±1.2 µM . ESI is also a potent inhibitor of protein translocation. The IC50 of ESI to ER translocation and N-glycosylation in vitro is ~70 µM .
ERAD pathway can eliminate misfolded ER proteins. Timely removing misfolded proteins from ER is involved in maintaining ER homeostasis . N-Glycosylation is the most common and versatile protein modification, it occurs at the β-amide of the aspargine of the Asn-Xaa-Ser/Thr sequon . ER mannosidase I could trigger the targeting of improperly folded glycoproteins to degradation .
In A9 cells, compared with Me2SO, treatment with EerI made polyubiquitinated MHC class I heavy chain (HC) accumulate in the cytosol. Compared with MG132, treatment with EerI resulted in very few deubiquitinated deglycosylated HC molecules, although a similar amount of accumulated polyubiquitinated HC . In H1299 cells, treatment with EerI for 24 hrs significantly (p< 0.01) reduced cell proliferation (24.0%) as compared to the vehicle-treated control .
On the 2nd day and the 6th day after the subcutaneous injection of H1299 cells (8×106) complexed with Matrigel, athymic nude mice were treated with EerI (10 µM). EerI treatment significantly reduced tumor growth as compared to the DMSO vehicle control .
. Benedict C. S. Cross, Craig McKibbin, Anna C. Callan, et al. Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum. Journal of Cell Science, 2009, 122:4393-4400.
. Qiuyan Wang, Bidhan A. Shinkre, Jin-gu Lee, et al. The ERAD Inhibitor Eeyarestatin I Is a Bifunctional Compound with a Membrane-Binding Domain and a
p97/VCP Inhibitory Group. PLoS ONE, 2010, 5(11):e15479.
. Shifra Ben-Dor, Nir Esterman, Eitan Rubin, et al. Biases and complex patterns in the residues flanking protein N-glycosylation sites. Glycobiology, 2004, 14(2):95-101.
. Myriam Ermonval, Claudia Kitzmüller, Anne Marie Mir, et al. N-glycan structure of a short-lived variant of ribophorin I expressed in the MadIA214 glycosylation-defective cell line reveals the role of a mannosidase that is not ER mannosidase I in the process of glycoprotein degradation. Glycobiology, 2001, 11(7):565-576.
. Qiuyan Wang, Lianyun Li and Yihong Ye. Inhibition of p97-dependent Protein Degradation by Eeyarestatin I. Journal of Biological Chemistry, 2008, 283(12):7445-7454.
. Christopher W. Valle, Taehong Min, Manish Bodas, et al. Critical Role of VCP/p97 in the Pathogenesis and Progression of Non-Small Cell Lung Carcinoma. PLoS ONE, 2011, 6(12): e29073.
|Physical Appearance||A crystalline solid|
|Storage||Store at -20°C|
|Solubility||Soluble in DMSO|
|Canonical SMILES||ClC1=CC=C(C=C1)N2[[email protected]@H](C(C)(C)N(CC(N/N=C/C=C\C3=CC=C([N+]([O-])=O)O3)=O)C2=O)N(C(NC(C=C4)=CC=C4Cl)=O)O|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|