Raphin1 acetate 是一种口服生物可利用的，选择性调节性磷酸酶 PPP1R15B (R15B) 抑制剂。Raphin1 acetate 与 R15B-PP1c 全磷酸酶强烈结合 (Kd=33 nM)，与 R15A-PP1c 相比，结合 R15B-PP1c 约为其 30 倍的选择性。Raphin1 acetate 穿过血脑屏障，并减少蛋白质错误折叠疾病的小鼠模型中的生物和分子缺陷。
货号:ajcx14934
CAS:2242616-04-0
分子式:C10H12Cl2N4O2
分子量：291.13
溶解度:DMSO: 41.67 mg/mL (143.13 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Raphin1 acetate is an orally bioavailable, selective inhibitor of the regulatory phosphatase PPP1R15B (R15B). Raphin1 acetate binds strongly to the R15B-PP1c holophosphatase (Kd=33 nM), and shows ~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].

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].

Raphin1 acetate improves weight of HD82Q 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 HD82Q mice[1].

[1]. Krzyzosiak A, et al. Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B. Cell. 2018 Aug 23;174(5):1216-1228.e19.