Salubrinal
目录号 : GC17331An inhibitor of eIF2α dephosphorylation
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
PC12 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.5-100 μM for 36 hours |
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Applications |
Salubrinal inhibited eIF2a dephosphorylation mediated by a herpes simplex virus protein and blocked viral replication. Salubrinal dose-dependently protected PC12 cells against endoplasmic reticulum (ER) stress-induced apoptosis. Moreover, Salubrinal induced eIF2α phosphorylation and selectively inhibited eIF2α dephosphorylation. |
| Animal experiment: | |
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Animal models |
Rat model; |
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Dosage form |
100 μM for 1-12 hours; i.c.v. administration |
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Applications |
Salubrinal increased deep slow wave sleep and reduced active waking compared with the vehicle. Salubrinal increased expression of p-eIF2α in the basal forebrain (BF) area, a sleep-wake regulatory brain region [2]. Moreover, Salubrinal induced sleep by activating sleep-promoting neurons and inhibiting wake-promoting neurons in the basal forebrain (BF) and hypothalamus [3]. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1Boyce, M., Bryant, K. F., Jousse, C., Long, K., Harding, H. P., Scheuner, D., Kaufman, R. J., Ma, D., Coen, D. M., Ron, D. and Yuan, J. (2005) A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science. 307, 935-939 2Methippara, M. M., Bashir, T., Kumar, S., Alam, N., Szymusiak, R. and McGinty, D. (2009) Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep. Am J Physiol Regul Integr Comp Physiol. 296, R178-184 3Methippara, M., Mitrani, B., Schrader, F. X., Szymusiak, R. and McGinty, D. (2012) Salubrinal, an endoplasmic reticulum stress blocker, modulates sleep homeostasis and activation of sleep- and wake-regulatory neurons. Neuroscience. 209, 108-118 | |
IC50: A cell-permeable and selective inhibitor of eIF2α dephosphorylation with an IC50 of 15 M.
The eukaryotic translation initiation factor 2 subunit α (eIF2α) is crucial in protein synthesis. eIF2α phosphorylation played an important role in protecting cells from apoptosis. Salubrinal selectively suppresses the phosphatase complexes that dephosphorylate eIF-2α. [1]
In vitro: This agent is reported to protect cells from endoplasmic reticulum (ER) stress-induced apoptosis (EC50 ~15 M) in PC12 cell lines induced with the protein glycosylation inhibitor tunicamycin and brefeldin A, which causes ER stress by blocking ER-to-Golgi vesicle transport. Salubrinal is a potentially useful agent to study mechanisms of ER stress-induced apoptosis. In addition, it was reported that salubrinal at 50 μM prevented cells from the autophagic and apoptotic progresses induced by loss of Bcl-2 function in murine leukemia L1210 cells. [1]
In vivo: Study from male ICR mice showed that salubrinal significantly aggravated the cisplatin-induced nephrotoxicity. In the kidneys of cisplatin-treated mice, the phosphorylation of eIF2α was significantly increased by salubrinal. In addition, the expression of CCAAT/enhancer binding protein, activating transcription factor 4 as well as the cleavage of caspases 3, 9 and 12 were also up-regulated. Moreover, salubrinal also increased the cisplatin-induced oxidative stress. These findings indicated that salubrinal aggravated cisplatin-induced nephrotoxicity via the up-regulation of ER stress-related cell apoptosis and oxidative stress. [2]
Clinical trial: So far, no clinical trial has been conducted.
References:
[1] Kessel D. Protection of Bcl-2 by salubrinal. Biochem Bioph Res Co. 2006; 346: 1320-3.
[2] Wu CT, Sheu ML, Tsai KS, Chiang CK and Liu SH. Salubrinal, an eIF2α dephosphorylation inhibitor, enhances cisplatin-induced oxidative stress and nephrotoxicity in a mouse model. Free Radic Biol Med, 2011; 51(3): 671-680.
| Cas No. | 405060-95-9 | SDF | |
| 化学名 | (E)-3-phenyl-N-[2,2,2-trichloro-1-(quinolin-8-ylcarbamothioylamino)ethyl]prop-2-enamide | ||
| Canonical SMILES | C1=CC=C(C=C1)C=CC(=O)NC(C(Cl)(Cl)Cl)NC(=S)NC2=CC=CC3=C2N=CC=C3 | ||
| 分子式 | C21H17Cl3N4OS | 分子量 | 479.81 |
| 溶解度 | ≥ 48mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0842 mL | 10.4208 mL | 20.8416 mL |
| 5 mM | 0.4168 mL | 2.0842 mL | 4.1683 mL |
| 10 mM | 0.2084 mL | 1.0421 mL | 2.0842 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。