Synonyms: (E)-2-(2-Chlorobenzylidene)hydrazinecarboximidamide; Sephin 1
Molecular Formula: C8H9ClN4
Molecular Weight: 196.64
Linear Structural Formula: C8H9ClN4
MDL Number: MFCD00790608
Purity: >=95% (HPLC)
Storage: 2-8C
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 alpha2-adrenergic activity. Phosphorylation of eIF2alpha, alpha 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 eIF2alpha, so inhibiting PPP1R15A activity prolongs the phosphorylation of eIF2alpha 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).