An adenosine analog which inhibits ribozyme self cleavage in mammalian cells, EC50 = 0.4 M (for expression of a luciferase reporter)1. A potent inhibitor of ER stress-induced XBP1 mRNA splicing2. It suppresses thapsigargin-, tunicamycin- and 2-deoxyglucose-induced XBP1 mRNA splicing in HeLa cells without affecting ATF6 and PERK activation. Although unable to inhibit IRE1 phosphorylation, it prevented IRE1-induced XBP1 mRNA cleavage in vitro. It inhibits not only ER stress-induced but also constitutive activation of XBP1 expression in multiple myeloma cell lines as well as in primary patient samples2. Displays synergistic effects with bortezomib. Inhibits unfolded protein response and induces apoptosis in pancreatic cancer cells3.
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