PKR Inhibitor

IC50: 186-210 nM

PKR Inhibitor is a double-stranded RNA-activated protein kinase (PKR) inhibitor.

Initiation of protein synthesis is reported to be regulated by kinase-dependent phosphorylation reactions. Double-stranded RNA-dependent protein kinase (PKR) is identified as one of these important kinases controlling the initiation step.

In vitro: PKR Inhibitor was identified as a small molecule able to inhibit the autophosphorylation of PKR and to rescue the translation blockade induced by PKR. It was found that PKR Inhibitor prevented not only PKR phosphorylation but also the activation of caspase 3 induced by Ab in SH-SY5Y cells. In addition, the protective effect of PKR Inhibitor on the neuronal cell death induced by endoplasmic reticulum-stress in SH-SY5Y cells has been reported [1].

In vivo: A previous animal study used an in-vivo model of 7-day-old rat exhibiting a high activation of brain PKR to investigate the effects of PKR Inhibitor. Results showed for the first time that acute systemic injection of PKR Inhibitor could specifically inhibit the apoptotic PKR/eIF2a signaling pathway without stimulating the proliferative mTOR/p70S6K signaling mechanism [1].

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] Ingrand, S. ,Barrier, L.,Lafay-Chebassier, C., et al. The oxindole/imidazole derivative C16 reduces in vivo brain PKR activation. FEBS Letters 581(23), 4473-4478 (2007).