Identification of natural products as inhibitors of the protein kinase RNA-like endoplasmic reticulum kinase to manage Alzheimer's disease

Abstract

Recently, the protein kinase RNA-like endoplasmic reticulum kinase PERK has been proposed as a potential target for Alzheimer's disease (AD) management, particularly after the detection of increased levels of phosphorylated PERK in the temporal cortex and the hippocampus of AD brain. Screening for PERK inhibitors led to the identification of the compound GSK2606414 (Figure 1) with IC50 of 3.2 nM and it was co-crystallized with the PERK kinase domain (PDB ID, 4G31). In this study, we used computational methods such as shape similarity, common chemical feature identification and docking simulation to search for and identify potential PERK inhibitors from natural product drug-like databases.