The activity of double-stranded RNA-activated protein kinase (PKR) is altered by viral infection as well as by various neuropathologies.[1],[2] A primary phosphorylation target of PKR is eukaryotic initiation factor 2 subunit α (eIF2α), blocking translation and driving apoptosis.3 PKR Inhibitor is an oxindole/imidazole derivative that binds the ATP-binding site of PKR and blocks autophosphorylation with an IC50 value of 186-210 nM.[3] PKR Inhibitor protects human neuroblastoma cells against cell damage triggered by tunicamycin-mediated endoplasmic reticulum stress.[4] It also prevents phosphorylation of Fas-associated protein with a death domain (FADD) in neuroblastoma cells, preventing FADD-dependent activation of caspases and apoptosis.[1] Intraperitoneal administration of PKR inhibitor in rats reduces phosphorylation of PKR and eIF2α in the brain.[5] Similar administration in mice enhances long-term memory storage, including contextual and auditory long-term fear memories.[2]

Reference:
[1]. Couturier, J., Morel, M., Pontcharraud, R., et al. Interaction of double-stranded RNA-dependent protein kinase (PKR) with the death receptor signaling pathway in amyloid β (Aβ)-treated cells and in APPSLPS1 knock-in mice. J. Biol. Chem. 285(2), 1272-1282 (2010).
[2]. Zhu, P.J., Huang, W., Kalikulov, D., et al. Suppression of PKR promotes network excitability and enhanced cognition by interferon-γ-mediated disinhibition. Cell 147(6), 1384-1396 (2011).
[3]. Jammi, N.V., Whitby, L.R., and Beal, P.A. Small molecule inhibitors of the RNA-dependent protein kinase. Biochemical and Biophysical Research Communications 308(1), 50-57 (2003).
[4]. Shimazawa, M., and Hara, H. Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage induced by ER stress. Neuroscience Letters 409(3), 192-195 (2006).
[5]. 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).