Selective inhibitor of IRE1alpha ribonuclease (RNase) activity (IC50 = 60 nM). Covalently binds to lysine 907 in the IRE1 endonuclease domain, blocking substrate access to the active site of IRE1alpha and inactivating both XBP1 splicing and IRE1alpha-mediated mRNA degradation but not IRE1 kinase activity1. Inhibits IRE1alpha in response to hypoxia or other ER stress-inducing agents but has no effect on proliferation or clonogenic survival of hypoxic cells2. Blocks production of IL-4, IL-5 and IL-13 production in T cells3. Prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production in pancreatic beta-cells4.
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