| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Sephin-1 targets the phosphatase regulatory subunit PPP1R15A (R15A). It selectively disrupts the PPP1R15A-PP1c complex, prolonging eIF2α phosphorylation after stress, delaying translation recovery, and attenuating the expression of stress genes such as the pro-apoptotic protein CHOP. It is devoid of PPP1R15B and α2-adrenergic activity.
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| ln Vitro |
During the day, oligodendrocytes' eIF2α phosphorylation is prolonged by cerguastat (5 μM) [1]. Holophosphatase phosphatase Icerguastat (Sephin1) selectively binds to and inhibits downstream-induced PPP1R15A, but not associated PPP1R15B, to prolong phosphosignal coupling Supplement and prevent other proteins' misfolded middle section from undergoing apoptosis [2].
In vitro, Sephin-1 selectively disrupts the PPP1R15A-PP1c complex, prolonging eIF2α phosphorylation after stress. It attenuates the expression of stress genes such as CHOP and protects cells from cytotoxic ER stress. It stimulates ATF4 synthesis in the absence of stress. |
| ln Vivo |
Icerguastat (4–8 mg/kg; intraperitoneally; daily for 35 days) postpones the body's reaction to experimental autoimmune encephalitis (EAE). Infection is prolonged once with iceraguastat (100 μg; ip). Premon
In vivo, Sephin-1 safely and selectively inhibits a regulatory subunit of protein phosphatase 1. It protects against protein misfolding, motor deficits, motor neuron loss, and the molecular defects in SOD1 mutant mice, a model of amyotrophic lateral sclerosis (ALS). Its cytoprotective effects have been observed in various neurodegenerative disease models. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays are not applicable for Sephin-1, as its target is a protein-protein interaction (PPP1R15A-PP1c). Its activity is assessed in cell-based assays measuring the disruption of this complex and the downstream effects on eIF2α phosphorylation and CHOP expression.
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| Cell Assay |
In vitro cellular assays for Sephin-1 are performed using cells subjected to ER stress. Cells are treated with the compound, and the phosphorylation of eIF2α and the expression of CHOP are measured by Western blot or qPCR. The compound's ability to protect cells from ER stress-induced cell death is assessed by measuring cell viability.
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| Animal Protocol |
Animal/Disease Models: C57BL/6J female mice were immunized with MOG35-55/CFA to induce chronic EAE[1]
Doses: 4 mg/kg, 8 mg/kg Route of Administration: Ip ;The lifetime of the virus in mice [3]. one time/day for 35 days Experimental Results: Both doses Dramatically delayed the onset of clinical disease, but the delay was greater with the 8 mg/kg treatment. Animal/Disease Models: Fiveweeks old female FVB mice (intracerebral injection of mouse-adapted RML prions) [3] Doses: 100 μg Route of Administration: intraperitoneal (ip) injection; 3 times a week for 60 days, treatment after 60 days Reduce to twice weekly intraperitoneal (ip) injections for 20 days. Experimental Results: Dramatically prolonged survival of prion-infected mice. In vivo animal studies for Sephin-1 are conducted in mouse models of neurodegenerative diseases, such as the SOD1 mutant mouse model of ALS. The compound is administered orally or intraperitoneally, and its effects on motor function, motor neuron survival, and molecular markers of stress are assessed. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Sephin-1 are not detailed in publicly available sources. As an orally active compound, it is expected to have good bioavailability and brain penetration, consistent with its effects on the central nervous system.
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| Toxicity/Toxicokinetics |
Toxicological data for Sephin-1 are not widely published. As a research compound, its safety profile has been evaluated in animal models. No significant toxicity has been reported in the available literature at the doses used in studies.
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| References |
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| Additional Infomation |
Icerguastat is an organic molecular entity with inhibitory properties. (Structure can be found in the first source.)
Sephin-1 is also known as Sephin1 and NSC-65390. It is a selective inhibitor of the integrated stress response (ISR). It is a Guanabenz analogue. It is being studied for its potential in treating neurodegenerative diseases. It is not an approved drug. |
| Molecular Formula |
C8H9N4CL
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|---|---|
| Molecular Weight |
196.637
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| Exact Mass |
196.051
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| Elemental Analysis |
C, 48.87; H, 4.61; Cl, 18.03; N, 28.49
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| CAS # |
951441-04-6
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| Related CAS # |
(E/Z)-Icerguastat;13098-73-2
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| PubChem CID |
9561611
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
374.2±44.0 °C at 760 mmHg
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| Flash Point |
180.1±28.4 °C
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| Vapour Pressure |
0.0±0.8 mmHg at 25°C
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| Index of Refraction |
1.626
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| LogP |
1.79
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
13
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| Complexity |
210
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(/C1C=CC=CC=1Cl)=N\NC(N)=N
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| InChi Key |
PDWJALXSRRSUHR-LFYBBSHMSA-N
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| InChi Code |
InChI=1S/C8H9ClN4/c9-7-4-2-1-3-6(7)5-12-13-8(10)11/h1-5H,(H4,10,11,13)/b12-5+
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| Chemical Name |
2-[(E)-(2-chlorophenyl)methylideneamino]guanidine
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| Synonyms |
Sephin1; Sephin-1; Sephin 1, icerguastatum; icerguastat
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~254.27 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (10.58 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT05508074
Conditions:Amyotrophic Lateral Sclerosis|ALSProducts are for research use only; We do not sell to patients
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