Sephin1 (Synonyms: NSC 65390) |
| Catalog No.GC12498 |
Sephin1 ((E/Z)-Sephin1) is a selective inhibitor of the phosphatase regulatory subunit PPP1R15A (R15A).
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Cas No.: 13098-73-2
Sample solution is provided at 25 µL, 10mM.
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Sephin1 is a selective inhibitor of stress-induced PPP1R15A and targets disease associated with accumulation of misfolded protein. [1]
PPP1R15A is a regulator subunit of protein phosphatase 1 and regulates stress-induced eIF2α (α subunit of eukaryotic translation initiation factor 2). It brings PP1 (serine/threonine-protein phosphatase) to dephosphorylate eIF2α. Phosphorylation of eIF2α reduces protein synthesis and prevents the accumulation of misfolded protein in ER (endoplasmic reticulum). Thus inhibiting PPP1R15A prolongs the phosphorylation of eIF2α, and benefits the treatment for protein misfolding disease. [1]
In cells treated with 5μm Sephin1 for 6 hours, Sephin1 specifically disrupted the PPP1R15A-PP1c complex without affecting PPP115B-PP1c complex. As a consequence, Sephin1 prolonged eIF2a phosphorylation in HeLa cells after stress (*2.5 μg/ml tunicamycin treatment) and delayed translational recovery. Sephin1 recused cell from cytotoxic ER stress* in wild-type cell but not the PPP1R15A mutant cell. [1]
In mice administrated orally with 1-5mg/kg Sephin1 for given time, Sephin1 exhibited no adverse effects on rotarod performances, total body weight gain or memory. Treating MPZ (Deletion of serine 63 of myelin protein zero) mutant mice with 1mg/kg orally twice a day, prevented the molecular, morphological and motor defects. Oral treatment of 5 mg/kg of Sephin1 once a day, prevented motor deficits, motor neuron loss and the molecular defects in SOD1 (Mutant and misfolding-prone superoxide dismutase 1) mutant mice. [1]
Reference:
[1].Das I, Krzyzosiak A, Schneider K, Wrabetz L, D'Antonio M, Barry N, Sigurdardottir A, Bertolotti A. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 2015 Apr 10; 348(6231):239-42.
| Cell experiment [1]: | |
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Cell lines |
HeLa and 293T cells |
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Preparation method |
Limited solubility. 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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Reaction Conditions |
6 h |
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Applications |
Sephin1 selectively disrupts the PPP1R15A-PP1c complex but leave the related PPP1R15B-PP1c complex unaffected. Thus Sephin1 prolongs eIF2a phosphorylation after stress, delays translation recover and attenuates expression of stress genes such as pro-apoptotic protein-CHOP. |
| Animal experiment [1]: | |
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Animal models |
SOD1 mice SOD1G93A in C57BL/6J |
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Dosage form |
5 mg/kg |
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Applications |
The progressive weight loss of SOD1 mutant mice and their motor deficits are almost completely prevented by 5 mg/kg of Sephin1 once a day, without adverse effects on weight gain or motor performance of wild-type mice. Sephin1 also prevents the motor deficits of SOD1 mutant mice that associated with motor neuron loss. |
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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: 1. Das I, Krzyzosiak A, Schneider K et al. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 2015 Apr 10;348(6231):239-42. |
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| Cas No. | 13098-73-2 | SDF | |
| Synonyms | NSC 65390 | ||
| Chemical Name | (E)-2-(2-chlorobenzylidene)hydrazinecarboximidamide | ||
| Canonical SMILES | ClC1=CC=CC=C1/C=N/NC(N)=N | ||
| Formula | C8H9ClN4 | M.Wt | 196.64 |
| Solubility | ≥ 7.75mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.0854 mL | 25.4272 mL | 50.8544 mL |
| 5 mM | 1.0171 mL | 5.0854 mL | 10.1709 mL |
| 10 mM | 0.5085 mL | 2.5427 mL | 5.0854 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
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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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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