PERK inhibitor 2

PERK inhibitor 2 (also known as PERK-IN-2) is a potent and selective small-molecule inhibitor of PKR-like endoplasmic reticulum kinase (PERK), an enzyme encoded by the EIF2AK3 gene. PERK is a key transmembrane protein in the endoplasmic reticulum (ER) that senses the accumulation of unfolded proteins and initiates the unfolded protein response (UPR) by phosphorylating the alpha subunit of eukaryotic initiation factor 2 (eIF2α). PERK inhibitor 2 inhibits this phosphorylation with an IC50 of 0.2 nM and demonstrates high selectivity (>100-fold) over other eIF2α kinases. Developed by Janssen Research and Development, the compound has been investigated in preclinical models of B-cell malignancies, including multiple myeloma and B-cell lymphoma, where it triggers a biphasic induction of ER stress and inhibits cell proliferation. Although it has demonstrated oral bioavailability and efficacy in mouse xenograft models (e.g., JIM-1), it is currently utilized exclusively as a research tool and is not approved for clinical use in humans.

Other names

PERK-IN-2PERK-IN2PERK-IN 2PERK inhibitor 2CAS 1337531-83-5CAS1337531-83-5CAS-1337531-83-5