Home >> Research Area >>Others>>eIF2a>> Salubrinal

Salubrinal

Selective eIF2α inhibitor CAS# 405060-95-9

Salubrinal

Catalog No. BCC4843----Order now to get a substantial discount!

Product Name & Size Price Stock
Salubrinal:10mg $180.00 In stock
Salubrinal:20mg $306.00 In stock
Salubrinal:50mg $720.00 In stock
Salubrinal:100mg $1260.00 In stock
Related Products

Quality Control of Salubrinal

Number of papers citing our products

Chemical structure

Salubrinal

3D structure

Chemical Properties of Salubrinal

Cas No. 405060-95-9 SDF Download SDF
PubChem ID 5717801 Appearance Powder
Formula C21H17Cl3N4OS M.Wt 479.81
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 100 mM in DMSO
Chemical Name (E)-3-phenyl-N-[2,2,2-trichloro-1-(quinolin-8-ylcarbamothioylamino)ethyl]prop-2-enamide
SMILES C1=CC=C(C=C1)C=CC(=O)NC(C(Cl)(Cl)Cl)NC(=S)NC2=CC=CC3=C2N=CC=C3
Standard InChIKey LCOIAYJMPKXARU-VAWYXSNFSA-N
Standard InChI InChI=1S/C21H17Cl3N4OS/c22-21(23,24)19(27-17(29)12-11-14-6-2-1-3-7-14)28-20(30)26-16-10-4-8-15-9-5-13-25-18(15)16/h1-13,19H,(H,27,29)(H2,26,28,30)/b12-11+
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.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Salubrinal

DescriptionCell-permeable, selective inhibitor of cellular phosphatase complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit α (eIF2α). Protects cells from endoplasmic reticulum stress-induced apoptosis (EC50 ~ 15 μM).

Protocol

Kinase Assay [1]
Phosphatase activities are determined on immunoprecipitates of the phosphatases. Briefly, 2×106 K562 cells are treated for 18 hr with Salubrinal (20 µM), PSI (10 nM), the combination of both drugs or okadaic acid (100 nM). After washing with PBS, cells are lysed for 15 min on ice either in PP1LB (for determination of PP1γ-activity; 20 mM Tris-HCl, pH 7.5, 1% Triton X-100, 10% glycerol, 132 mM NaCl, Roche complete protease inhibitor ) or in RIPA (for PP2A), supplemented with Roche complete protease inhibitor). Cell lysates containing 500 µg (PP1γ) or 300 µg (PP2A) protein are immunoprecipitated overnight at 4°C with 2-3 µg of the appropriate antibodies and then incubated with Protein A-Sepharose. Immunoprecipitates are washed three times in lysis buffer, followed by resuspension in phosphatase assay buffer (PP2A: 20 mM Tris-HCl, pH7.5, 0.1 mM CaCl2; PP1γ: 50 mM Tris HCl pH 7.0, 0.2 mM MnCl2, 0.1 mM CaCl2, 125 µg/mL BSA, 0.05% Tween 20), supplemented with 100 µM 6,8-difluoro-4-methyl-umbelliferyl phosphate (DiFMUP). Precipitates are allowed to react with substrate for 1 hr at 37°C on an Eppendorf Thermoshaker, centrifuged and DiFMU fluorescence is measured on a BioTek Lambda Fluoro 320 microplate reader (360 nmex/460 nmem). Phosphatase activities are given as percent change relative to the control (DMSO treated cells)[1].

Cell Assay [1]
Cellular viability is assessed by the WST-1 colorimetric assay. Assays are performed on 96 well plates with 2×104 K562 cells/well in triplicate with Salubrinal concentrations ranging from 5-75 µM (total volume of 200 µL, 18 hrs). Untreated cells served as negative control sample[1].

Animal Administration [2]
Mice[2] Using Balb/c female mice (~nine weeks old), CAIA is induced by intravenous injection of a 2 mg cocktail of ArthritoMAb antibodies on day 0 followed by intraperitoneal injection of 100 µg LPS on day 3. Mice are randomly divided into a placebo group and a Salubrinal-treated group. Salubrinal (2.0 mg/kg) is intravenously administered daily from day 0, while a solvent (49.5% PEG 400 and 0.5% Tween 80 in PBS) is administered to the placebo group.

References:
[1]. Drexler HC. Synergistic Apoptosis Induction in Leukemic Cells by the Phosphatase Inhibitor Salubrinal and Proteasome Inhibitors. PLoS One. 2009;4(1):e4161. [2]. Hamamura K, et al. Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis. Cell Signal. 2015 Apr;27(4):828-35.

Salubrinal Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Salubrinal Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of Salubrinal

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.0842 mL 10.4208 mL 20.8416 mL 41.6832 mL 52.104 mL
5 mM 0.4168 mL 2.0842 mL 4.1683 mL 8.3366 mL 10.4208 mL
10 mM 0.2084 mL 1.0421 mL 2.0842 mL 4.1683 mL 5.2104 mL
50 mM 0.0417 mL 0.2084 mL 0.4168 mL 0.8337 mL 1.0421 mL
100 mM 0.0208 mL 0.1042 mL 0.2084 mL 0.4168 mL 0.521 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on Salubrinal

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.

Featured Products
New Products
 

References on Salubrinal

Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway.[Pubmed:28152298]

Mol Cells. 2017 Jan;40(1):66-72.

Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-alpha, the key signaling process in the ERS pathway. In this study, the effects of Salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with Salubrinal (0.5 mg.kg(-1).day(-1)) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that Salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling.

Synergistic antitumor activity of the combination of salubrinal and rapamycin against human cholangiocarcinoma cells.[Pubmed:27863431]

Oncotarget. 2016 Dec 20;7(51):85492-85501.

Less is known about the roles of eukaryotic initiation factor alpha (eIF2alpha) in cholangiocarcinoma (CCA). Here, we report that eIF2alpha inhibitor Salubrinal inhibits the proliferation of human CCA cells. Clinical application of mammalian target of rapamycin (mTOR) inhibitors only has moderate antitumor efficacy. Therefore, combination approaches may be required for effective clinical use of mTOR inhibitors. Here, we investigated the efficacy of the combination of Salubrinal and rapamycin in the treatment of CCA. Our data demonstrate a synergistic antitumor effect of the combination of Salubrinal and rapamycin against CCA cells. Rapamycin significantly inhibits the proliferation of CCA cells. However, rapamycin initiates a negative feedback activation of Akt. Inhibition of Akt by Salubrinal potentiates the efficacy of rapamycin both in vitro and in vivo. Additionally, rapamycin treatment results in the up-regulation of Bcl-xL in a xenograft mouse model. It is notable that Salubrinal inhibits rapamycin-induced Bcl-xL up-regulation in vivo. Taken together, our data suggest that Salubrinal and rapamycin combination might be a new and effective strategy for the treatment of CCA.

Salubrinal protects against Clostridium difficile toxin B-induced CT26 cell death.[Pubmed:28119311]

Acta Biochim Biophys Sin (Shanghai). 2017 Mar 1;49(3):228-237.

Clostridium difficile (C. difficile) is considered to be the major cause of the antibiotic-associated diarrhea and pseudomembranous colitis in animals and humans. The prevalence of C. difficile infections (CDI) has been increasing since 2000. Two exotoxins of C. difficile, Toxin A (TcdA) and Toxin B (TcdB), are the main virulence factors of CDI, which can induce glucosylation of Rho GTPases in host cytosol, leading to cell morphological changes, cell apoptosis, and cell death. The mechanism of TcdB-induced cell death has been investigated for decades, but it is still not completely understood. It has been reported that TcdB induces endoplasmic reticulum stress via PERK-eIF2alpha signaling pathway in CT26 cell line (BALB/C mouse colon tumor cells). In this study, we found that Salubrinal, a selective inhibitor of eIF2alpha dephosphorylation, efficiently protects CT26 cell line against TcdB-induced cell death and tried to explore the mechanism underlying in this protective effect. Our results demonstrated that Salubrinal protects CT26 cells from TcdB-mediated cytotoxic and cytopathic effect, inhibits apoptosis and death of the toxin-exposed cells via caspase-9-dependent pathway, eIF2alpha signaling pathway, and autophagy. These findings will be helpful for the development of CDI therapies.

A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.[Pubmed:15705855]

Science. 2005 Feb 11;307(5711):935-9.

Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified Salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, Salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.

Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative.[Pubmed:16002288]

Bioorg Med Chem Lett. 2005 Sep 1;15(17):3849-52.

The synthesis and structure-activity relationships (SAR) of Salubrinal, a small molecule that protects cells from apoptosis induced by endoplasmic reticulum (ER) stress, are described. It is revealed that the trichloromethyl group greatly contributes to the activity. Based on the SAR results, Salubrinal was converted into a biotinylated derivative which retains activity and can be used as a biological tool for target identification.

Description

Salubrinal is a selective inhibitor of eIF2α dephosphorylation and inhibits ER stress-mediated apoptosis with EC50 of ~15 μM in a cell-free assay.

Keywords:

Salubrinal,405060-95-9,Natural Products,eIF2a, buy Salubrinal , Salubrinal supplier , purchase Salubrinal , Salubrinal cost , Salubrinal manufacturer , order Salubrinal , high purity Salubrinal

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: