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Biological Activity:

Sephin1 is a potent, selective and bioavailable inhibitor of the regulatory subunit PPP1R15A of protein phosphatase 1. It selectively bound and inhibited 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. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Sephin1 could be a very good chemical tool to prevent proteostasis diseases by selective inhibition of a phosphatase regulatory subunit.

How to Use:

In vitro: Sephin1 was used at 0.1-1 µM final concentration in vitro and in cellular assays.
In vivo: Sephin1 was orally dosed to MPZmutant mice or SOD1mutant mice at 1 mg/Kg twice a day.

Reference:

• 1. Das I, et al. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. (2015) Science. 348(6231):239-42.