| Bioactivity | Icerguastat (Sephin1), a derivative of Guanabenz lacking the α2-adrenergic activity, is a selective inhibitor of the phosphatase regulatory subunit PPP1R15A (R15A). Icerguastat inhibits eIF2α dephosphorylation, thereby prolonging the protective response. Anti-prion effect[1][2][3]. |
| Invitro | Icerguastat (5 µM) prolongs eIF2α phosphorylation in oligodendrocytes under stress[1].Icerguastat (Sephin1) (selective inhibitor of a holophosphatase), safely and selectively inhibits a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively binds and inhibits the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress[2]. |
| 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: |
| Name | Icerguastat |
| CAS | 951441-04-6 |
| Formula | C8H9ClN4 |
| Molar Mass | 196.64 |
| Appearance | Solid |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| Reference | [1]. Chen Y, et al. Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis. Brain. 2019;142(2):344-361. [2]. Das I, et al. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 2015;348(6231):239-242. [3]. Thapa S, et al. Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model. Mol Neurobiol. 2020;57(5):2206-2219. |