HY-15486-5mg | Salubrinal [405060-95-9] Clinisciences

Beschreibung

Salubrinal is a cell-permeable and selective inhibitor of eIF2α dephosphorylation^[1]. Salubrinal acts as a dual-specificity phosphatase 2 (Dusp2) inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis^[2]. Salubrinal has antiviral activity against HSV-1 and inhibits dephosphorylation of eIF2α mediated by the HSV-1 protein ICP34.5^[3].

IC₅₀ & Target^[1]^[3]

Dusp2

HSV-1

Cellular Effect

Cell Line	Type	Value	Description	References
PC-12	EC₅₀	15 μM Compound: 1	Cytoprotective activity on rat tunicamycin treated rat pheochromocytoma cell line PC12 from apoptosis induced by Endoplasmic reticulum stress Cytoprotective activity on rat tunicamycin treated rat pheochromocytoma cell line PC12 from apoptosis induced by Endoplasmic reticulum stress	[PMID: 16002288]

In Vitro

Salubrinal, a recently identified PP1 inhibitor capable to protect against endoplasmic reticulum (ER) stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal preferentially seems to target the PP1/GADD34 complex, Salubrinal is of interest to examine whether the effect of Salubrinal could also be recapitulated by another inhibitor of this phosphatase. For this purpose cantharidin, wis selected, which is less toxic than okadaic acid, but which also blocks PP1 (IC₅₀=1.7 μM) activities^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Salubrinal significantly suppresses inflammation of the paws of CAIA mice. For instance, the clinical scores are 1.94±1.7 (placebo) and 0.31±0.6 (Salubrinal) on day 6; and 4.63±3.4 (placebo) and 1.09±1.6 (Salubrinal) on day 12. Consistent with the clinical scores, the thickening of the paws is also reduced in the Salubrinal-treated group. Furthermore, Salubrinal reduces the histological scores from 1.47±1.10 (N=16; placebo) to 0.59±0.64 (N=16; Salubrinal) (p=0.01)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molekulargewicht

479.80

Formel

C₂₁H₁₇Cl₃N₄OS

CAS. Nr.

405060-95-9

Appearance

Solid

Color

Light brown to gray

SMILES

O=C(NC(NC(NC1=CC=CC2=C1N=CC=C2)=S)C(Cl)(Cl)Cl)/C=C/C3=CC=CC=C3

Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

4°C, protect from light

*In solvent : -80°C, 2 years; -20°C, 1 year (protect from light)

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 50 mg/mL (104.21 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.0842 mL	10.4210 mL	20.8420 mL
5 mM	0.4168 mL	2.0842 mL	4.1684 mL
10 mM	0.2084 mL	1.0421 mL	2.0842 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (protect from light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molaritätsrechner
Verdünnungsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 45% PEG300 5% Tween-80 50% Saline
Solubility: 10 mg/mL (20.84 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

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(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

Reinheit & Dokumentation

Purity: 99.58%

Select Batch:

SDS (393 KB)

COA (249 KB) HNMR (183 KB) RP-HPLC (206 KB)

Handling Instructions (2659 KB)

Verweise

[1]. Drexler HC. Synergistic Apoptosis Induction in Leukemic Cells by the Phosphatase Inhibitor Salubrinal and Proteasome Inhibitors. PLoS One. 2009;4(1):e4161. [Content Brief]

[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. [Content Brief]

[3]. Bryant KF, et al. ICP34.5-dependent and -independent activities of salubrinal in herpes simplex virus-1 infected cells. Virology. 2008 Sep 30;379(2):197-204. [Content Brief]

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 nm_ex/460 nm_em). Phosphatase activities are given as percent change relative to the control (DMSO treated cells)^[1]. MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Zellassay ^[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]. MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Tierverwaltung ^[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. MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Verweise	[1]. Drexler HC. Synergistic Apoptosis Induction in Leukemic Cells by the Phosphatase Inhibitor Salubrinal and Proteasome Inhibitors. PLoS One. 2009;4(1):e4161. [Content Brief] [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. [Content Brief] [3]. Bryant KF, et al. ICP34.5-dependent and -independent activities of salubrinal in herpes simplex virus-1 infected cells. Virology. 2008 Sep 30;379(2):197-204. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.0842 mL	10.4210 mL	20.8420 mL	52.1050 mL
	5 mM	0.4168 mL	2.0842 mL	4.1684 mL	10.4210 mL
	10 mM	0.2084 mL	1.0421 mL	2.0842 mL	5.2105 mL
	15 mM	0.1389 mL	0.6947 mL	1.3895 mL	3.4737 mL
	20 mM	0.1042 mL	0.5211 mL	1.0421 mL	2.6053 mL
	25 mM	0.0834 mL	0.4168 mL	0.8337 mL	2.0842 mL
	30 mM	0.0695 mL	0.3474 mL	0.6947 mL	1.7368 mL
	40 mM	0.0521 mL	0.2605 mL	0.5211 mL	1.3026 mL
	50 mM	0.0417 mL	0.2084 mL	0.4168 mL	1.0421 mL
	60 mM	0.0347 mL	0.1737 mL	0.3474 mL	0.8684 mL
	80 mM	0.0261 mL	0.1303 mL	0.2605 mL	0.6513 mL
	100 mM	0.0208 mL	0.1042 mL	0.2084 mL	0.5211 mL

Salubrinal Related Classifications

Metabolic Enzyme/Protease Anti-infection Autophagy Apoptosis
Phosphatase HSV Autophagy Apoptosis

Salubrinal [405060-95-9]

Katalog-Nummer HY-15486-5mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Alle HSV Isoform-spezifische Produkte anzeigen:

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

Salubrinal Related Classifications

Keywords:

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Salubrinal [405060-95-9]

Katalog-Nummer HY-15486-5mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Alle HSV Isoform-spezifische Produkte anzeigen:

Salubrinal Related Antibodies

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

Salubrinal Related Classifications

Keywords:

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