Synonyms: IFB-088 | IFB088 | Sephin-1 | Sephin1
Compound class:
Synthetic organic
Comment: Icerguastat (IFB-088, Sephin1) selectively inhibits the regulatory subunit PPP1R15A within the PPP1R15A/PP1c phosphatase complex [2]. Inhibiting PPP1R15A results in reduced dephosphorylation of the translation initiation factor eIF2α, which rescues cells from proteostasis collapse. Structurally icerguastat is a guanabenz derivative but it has no α2-adrenerceptor agonist activity. Icerguastat is designed to maintain an active integrated stress response as a cytoprotective mechanism to combat the toxic effects of cellular stress [1].
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References |
1. Chen Y, Podojil JR, Kunjamma RB, Jones J, Weiner M, Lin W, Miller SD, Popko B. (2019)
Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis. Brain, 142 (2): 344-361. [PMID:30657878] |
2. Das I, Krzyzosiak A, Schneider K, Wrabetz L, D'Antonio M, Barry N, Sigurdardottir A, Bertolotti A. (2015)
Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science, 348 (6231): 239-42. [PMID:25859045] |