Salubrinal

Catalog No.S2923

For research use only.

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

Salubrinal Chemical Structure

CAS No. 405060-95-9

Selleck's Salubrinal has been cited by 29 publications

Purity & Quality Control

Choose Selective PERK Inhibitors

Biological Activity

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.
Targets
eIF2α [1]
(Cell-free assay)
In vitro

Salubrinal is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit α (eIF2α). Salubrinal inhibited ER stress-mediated apoptosis induced by the protein glycosylation inhibitor tunicamycin (Tm) in a dose-dependent manner, with a median effective concentration (EC50) ∼ 15 μM. Salubrinal also suppressed Tm-induced DNA fragmentation the processing of caspase-7, a caspase activated by ER stress. However, Salubrinal is not a general apoptosis inhibitor. Salubrinal induced rapid and robust eIF2α phosphorylation and its downstream effects in PC12 cells, including down-regulation of cyclin D1 and up-regulation of GADD34 and CHOP, two proteins whose expression is induced by eIF2α phosphorylation. Salubrinal inhibits eIF2α dephosphorylation by inhibiting the PP1/GADD34 complex. Salubrinal inhibits HSV replication with IC50 of ~ 3μM by inhibiting eIF2α dephosphorylation. [1] Salubrinal increased non-rapid eye movement (NREM) sleep. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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Ramos-2G6-4C10 NVHmTnB1T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MY\Jcohq[mm2aX;uJI9nKGi3bXHuJHJidW:|LULHOk01SzFyIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTBiPTC5MlkxOzF3IN88UU4> NGrmUVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkevK|5USU6JRWK8M4E,
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Assay
Methods Test Index PMID
Western blot ATF4 ; HSF1 / p-HSF1 / ATF3 / c-fos / NFATc1 / RelA ; GRP78 / p-eIF2α / CHOP 27729194 27189267 24525736
In vivo Salubrinal inhibits HSV replication in a mouse cornea infection model. Compared to vehicle control, topical Salubrinal treatment significantly reduced the viral titer recovered from eye swabs of infected animals. [1] I.C.V. administration of Salubrinal significantly modified the homeostatic sleep response. [3]

Protocol (from reference)

Cell Research:[1]
  • Cell lines: PC12
  • Concentrations: 0-100 μM
  • Incubation Time: 48 hours
  • Method: PC12 cells are plated in 384-well plates at 5000 cells per well in 40μL phenol red-freemedium containing 3μg/ml Tm to induce ER stress. 100 nL of the DiverSet E (5 mg/mlin DMSO) or National Cancer Institute’s (NCI) Structural Diversity set and Open Collections (10 mM in DMSO) (NCI) are added to the wells by robotic pin transfer. After 48 hours, cell viability is assessed using a luminescence-based ATP assay. DMSO- and zVAD.fmk-treated wells on each plate served as negative and positive controls for rescue from ER stress-induced ATP loss, respectively.
Animal Research:[1]
  • Animal Models: Eight-week-old male CD-1 outbred mice
  • Dosages: 75μM
  • Administration: On cornea

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 479.81
Formula

C21H17Cl3N4OS

CAS No. 405060-95-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC=C(C=C1)C=CC(=O)NC(C(Cl)(Cl)Cl)NC(=S)NC2=CC=CC3=C2N=CC=C3

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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