Structural determinants of PERK inhibitor potency and selectivity.

ABSTRACT: The unfolded protein response (UPR) is a coordinated program that promotes cell survival under conditions of endoplasmic reticulum stress and is required in tumor progression as well. To date, no specific small molecule inhibitor targeting this pathway has been identified. Pancreatic endoplasmic reticulum kinase (PERK), one of the UPR transducers, is an eIF2α kinase. Compromising PERK function inhibits tumor growth in mice, suggesting that PERK may be a cancer drug target, but identifying a specific inhibitor of any kinase is challenging. The goal of this study was to identify some pair-wise receptor-ligand atomic contacts that confer selective PERK inhibition. Compounds selectively inhibiting PERK-mediated phosphorylation in vitro were identified using an initial virtual library screen, f

SUBMITTER: Wang H 

PROVIDER: S-EPMC3058854 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature