Raphin1 Acetate is a selective, R15B inhibitor which caused a rapid and transient accumulation of its phosphorylated substrate like eIF2α, resulting in a transient attenuation of protein synthesis in cells. Raphin1 was orally bioavailable, crossed the blood-brain barrier, and demonstrated efficacy in a mouse model of Huntington’s disease.
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Raphin1 acetate, an orally bioavailable, selective PPP1R15B (R15B) regulatory phosphatase inhibitor, binds tightly to the R15B-PP1c holophosphatase (KD=33 nM). It demonstrates approximately 30-fold greater selectivity for R15B-PP1c over R15A-PP1c. Capable of crossing the blood-brain barrier, Raphin1 acetate mitigates both organismal and molecular impairments in a mouse model of protein misfolding disease[1].
Raphin1 acetate 动物研究
Animal study
Raphin1 acetate enhances the weight of HD82Q mice treated orally with 2 mg/kg daily from ages 4 to 10 weeks. It also reduces SDS-insoluble huntingtin assemblies and nuclear inclusions in the cortex of HD82Q mice[1].
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