SAR439883 (SAR 439883) is a novel potent, selective, orally active PKR inhibitor with IC50 of 0.68/0.69 uM against hPKR/mPKR, respectively.
SAR439883 dose-dependently ameliorated the AβO-induced cognitive impairment in both Y-maze and Morris Water Maze, prevented loss of synaptic proteins, and reduced levels of the proinflammatory cytokine interleukin-1β In both mouse models.
SAR439883 rescued memory deficits and prevented neurodegeneration in animal models of AD-like pathology, suggesting that inhibition of PKR is a potential therapeutic approach for AD.
