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| 25mg |
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Eeyarestatin I is a novel and potent ERAD (endoplasmic reticulum-associated protein degradation) inhibitor and protein translocation inhibitor with anticancer activity. Acting to induce tumor cell death and disturb ER homeostasis by blocking membrane-bound p97.
| Targets |
Endoplasmic reticulum-associated protein degradation (ERAD)
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|---|---|
| ln Vitro |
A549 and H358 cells treated with eeyarestatin I (2.5–40 μM; 48 hours) experience quantitative essential cell death [1]. Treatment of A549 and H358 cells with eeyarestatin I (2.5–40 μM; 48 hours) resulted in a rise in endoplasmic reticulum (ER) intermediate markers, including Bip and CHOP at as low as 20 μM. Important proteins, such as IRE1α and PERK, are ubiquitinated in a dose-dependent manner when treated with eeyarestatin I[1]. Treatment with eeyarestatin I (20 μM; 48 hours; A549 and H358 cells) causes cell invasion and migration [1]. By most likely deactivating the Sec61 complex, eeyarestatin 1 inhibits the transfer of immature proteins from membrane complexes to the ER translocation machinery [2]. Assay for viability [1]
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| Cell Assay |
Viability assay [1]
Cell Types: A549 and H358 cells Tested Concentrations: 2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM Incubation Duration: 48 hrs (hours) Experimental Results: Caused dose-dependent cell death of A549 and H358 cells. Western Blot Analysis[1] Cell Types: A549 and H358 Cell Tested Concentrations: 2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased ER stress markers including Bip and CHOP. |
| References |
[1]. Parag P Shah, et al. Regulation of VCP/p97 demonstrates the critical balance between cell death and epithelial-mesenchymal transition (EMT) downstream of ER stress. Oncotarget. 2015 Jul 10;6(19):17725-37.
[2]. Benedict C S Cross, et al. Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum. J Cell Sci. 2009 Dec 1;122(Pt 23):4393-400. [3]. Qiuyan Wang, et al. Inhibition of p97-dependent protein degradation by Eeyarestatin I. J Biol Chem. 2008 Mar 21;283(12):7445-54. [4]. Qiuyan Wang, et al. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2200-5. [5]. Pauwels E, et al. Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway. Int J Mol Sci. 2021 Nov 5;22(21):12007. |
| Molecular Formula |
C27H25CL2N7O7
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|---|---|
| Molecular Weight |
630.436103582382
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| Exact Mass |
629.12
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| CAS # |
412960-54-4
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| Appearance |
Powder
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| SMILES |
CC1(C(N(C(=O)N1CC(=O)NN=CC=CC2=CC=C(O2)[N+](=O)[O-])C3=CC=C(C=C3)Cl)N(C(=O)NC4=CC=C(C=C4)Cl)O)C
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| InChi Key |
JTUXTPWYZXWOIB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H25Cl2N7O7/c1-27(2)24(35(40)25(38)31-19-9-5-17(28)6-10-19)34(20-11-7-18(29)8-12-20)26(39)33(27)16-22(37)32-30-15-3-4-21-13-14-23(43-21)36(41)42/h3-15,24,40H,16H2,1-2H3,(H,31,38)(H,32,37)
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| Chemical Name |
2-[3-(4-chlorophenyl)-4-[(4-chlorophenyl)carbamoyl-hydroxyamino]-5,5-dimethyl-2-oxoimidazolidin-1-yl]-N-[3-(5-nitrofuran-2-yl)prop-2-enylideneamino]acetamide
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| Synonyms |
Eeyarestatin I
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 25~85 mg/mL (39.7~134.8 mM)
Ethanol: ~7 mg/mL (~11.1 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (1.98 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5862 mL | 7.9310 mL | 15.8619 mL | |
| 5 mM | 0.3172 mL | 1.5862 mL | 3.1724 mL | |
| 10 mM | 0.1586 mL | 0.7931 mL | 1.5862 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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