Raphin1 (acetate)

2242616-04-0

291.13

DMSO : 41.67 mg/mL (143.13 mM; Need ultrasonic)

Metabolic Enzyme/Protease

Raphin1 acetate is an orally bioavailable, selective inhibitor of the regulatory phosphatase PPP1R15B (R15B). Raphin1 acetate binds strongly to the R15B-PP1c holophosphatase (K_d=33 nM), and shows ca.30-fold selective in binding R15B-PP1c over R15A-PP1c. Raphin1 acetate crosses the blood-brain barrier, and reduces organismal and molecular deficits in a mouse model of a protein misfolding disease^[1]. IC50 & Target: Kd: 33 nM (R15B-PP1c holophosphatase)^[1] In Vitro: Raphin1 acetate causes a rapid and transient accumulation of its phosphorylated substrate, resulting in a transient attenuation of protein synthesis^[1].
Raphin1 acetate inhibits the recombinant R15B-PP1c holoenzyme, but not the closely related R15A-PP1c, by interfering with substrate recruitment^[1]. In Vivo: Raphin1 acetate improves weight of HD^82Q mice treated from 4 to ?10 weeks of age with 2 mg/kg of Raphin1 once a day by oral gavage. Raphin1 acetate also decreases SDS-insoluble huntingtin assemblies and nuclear inclusions in the cortex of HD^82Q mice^[1].