| Identification | Back Directory | [Name]
Sephin 1 | [CAS]
951441-04-6 | [Synonyms]
Sephin 1
lcerguastat
Icerguastat
Sephin 1 - NSC 65390
2-[(E)-(2-chlorophenyl)methylideneamino]guanidine
Hydrazinecarboximidamide, 2-[(2-chlorophenyl)methylene]-, (2E)- | [Molecular Formula]
C8H9ClN4 | [MDL Number]
MFCD00790608 | [MOL File]
951441-04-6.mol | [Molecular Weight]
196.64 |
| Chemical Properties | Back Directory | [Boiling point ]
320.9±44.0 °C(Predicted) | [density ]
1.35±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Soluble in DMSO (100 mM) | [form ]
powder | [pka]
8.74±0.30(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Uses]
Sephin 1 is a selective inhibitor of holophosphatase, a regulatory subunit of protein phosphatase 1. May be used in the prevention of protein misfolding diseases. | [Biochem/physiol Actions]
Sephin1 is a selective inhibitor of a holophosphatase. It is a guanabez derivative that binds to and inhibits a regulatory subunit of the stress-induced protein phosphatase 1 (PPP1R15A), but not the constitutive PPP1R15B, and lacks α2-adrenergic activity. Phosphorylation of eIF2α, α subunit of eukaryotic translation initiation factor 2, reduces protein synthesis and prevents the accumulation of misfolded protein in the endoplasmic reticulum (ER). PPP1R15A recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate eIF2α, so inhibiting PPP1R15A activity prolongs the phosphorylation of eIF2α and aids in its prevention of the accumulation of misfolded protein. In vitro Sephin1 protected cells from lethal protein misfolding and cytotoxic ER stress. In vivo sephin1 prevented two unrelated protein misfolding diseases in mice (Charchot-Marie-Tooth 1B and ALS). | [in vivo]
Icerguastat (4-8 mg/kg; i.p.; daily for 35 days) delays the onset of EAE (experimental autoimmune encephalomyelitis)[1].
Icerguastat (100 μg; i.p.) prolongs the survival of prion-infected mice[3]. | Animal Model: | C57BL/6J female mice immunized with MOG35-55/CFA to induce chronic EAE[1] | | Dosage: | 4 mg/kg, 8 mg/kg | | Administration: | I.p.; daily for 35 days | | Result: | Significantly delayed clinical disease onset with both dosages, but to a greater extent with the 8 mg/kg treatment.
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| Animal Model: | Five-week-old female FVB mice (intracerebrally with mouse-adapted RML prions)[3] | | Dosage: | 100 μg | | Administration: | I.p.; 3 times per week for 60 days, after 60 days of treatment, the treatment was reduced to two i.p. injections per week for another 20 days. | | Result: | Significantly prolonged survival of prion-infected mice.
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| [storage]
+4°C |
|
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
|