Icerguastat (Sephin1) ，一种缺乏 α2-肾上腺素能活性的 Guanabenz 衍生物，是磷酸酶调节亚单位 PPP1R15A (R15A) 的选择性抑制剂。Icerguastat 抑制 eIF2α 去磷酸化，从而延长保护反应。Icerguastat 具有抗朊病毒作用。
货号:ajcx34198
CAS:951441-04-6
分子式:C8H9ClN4
分子量：196.64
溶解度:DMSO : 250 mg/mL (1271.36 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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].

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].

[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.