Toyocamycin
Unfolded protein response (UPR) inhibitor / An adenosine analog which inhibits ribozyme self cleavage in mammalian cells, EC50 = 0.4 uM (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 IRE1α phosphorylation, it prevented IRE1α-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.
Biochemicals & reagents
606-58-6
7-Deaza-7-cyanoadenosine; NSC 63701; NSC 99843; Neuro 000027; Unamycin B; Vengicide
1) Yen et al. (2006), Identification of inhibitors of ribozyme self-cleavage in mammalian cells via high-throughput screening of chemical libraries; RNA, 12 797 2) Ri et al. (2012), Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing; Blood Cancer J., 2 e79 3) Chien et al. (2014), Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells; Oncotarget, 5 4881
-20°C
TARGET: UPR (Unfolded protein response); RNA -- PATHWAY: Apoptosis inducer; Degradation -- RESEARCH AREA: Ubiquitin/Proteasome; Neuroscience; Cellular stress; Cell death -- DISEASE AREA: Cancer; NeurodegenerationInfectious disease