APY29

Biochem/physiol Actions

APY29 is a small molecule that inhibits the kinase activity of IRE1α (in vitro autophosphorylation IC50 = 280 nM) by targeting its active site ATP-binding pocket, while simultaneously acting as an allosteric activator of IRE1α RNase activity (EC50 = 460 nM) by keeping the active site in an open conformation. When applied 1 hr prior to stress induction by 4-hr 6 nM thapsigargin treatment, APY29 significantly potentiates stress-induced unfolded protein response (UPR) in rat insulinoma INS-1 cultures (XBP1 mRNA processing induction = 54% without vs. 78% with 1-hr 3 µM APY29 pretreatment).

APY29 has the ability to enhance inositol requiring kinase enzyme 1 α (IRE1α) (P830L)′s oligomeric state to rescue RNase activity.

General description

APY29 is considered as a type I kinase inhibitor of inositol requiring kinase enzyme 1 α (IRE1α).