Catalog No.: PC-35503Not For Human Use, Lab Use Only.
Raphin1 (PPP1R15B inhibitor Raphin1) is a potent, selective, BBB-penetrant, orally bioavailable inhibitor of regulatory subunit of protein phosphatase 1, PPP1R15B, binds to the R15B-PP1c holophosphatase with Kd of 33 nM, 30-fold selective in binding R15B-PP1c over R15A-PP1c and did not bind to PP1c.
Raphin1 (PPP1R15B inhibitor Raphin1) is a potent, selective, BBB-penetrant, orally bioavailable inhibitor of regulatory subunit of protein phosphatase 1, PPP1R15B, binds to the R15B-PP1c holophosphatase with Kd of 33 nM, 30-fold selective in binding R15B-PP1c over R15A-PP1c and does not bind to PP1c.
Raphin1 at 10 uM selectively inhibits R15B, but not R15A, in cells in the holophosphatase SPR assay, inducing a transient increase of eIF2a phosphorylation and attenuation of protein synthesis.
Raphin1 inhibits dephosphorylation of eIF2a by R15B-PP1c, but not by R15APP1c, promotes proteasome- and p97-dependent degradation of R15B.
Raphin1 demonstrates efficacy in a mouse model of Huntington’s disease in vivo.
1. Agnieszka Krzyzosiak, et al. Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B. Cell. July 26, 2018DOI:https://doi.org/10.1016/j.cell.2018.06.030.
