Toyocamycin (hydrate)

Toyocamycin is a natural adenosine analog first isolated from Streptomyces and shown in early studies to be cytotoxic to bacteria, fungi, and cancer cells and to have antiviral activities. Toyocamycin prevents IRE1α-induced mRNA cleavage (IC₅₀ = 80 nM) and inhibits constitutive activation of XBP1 in multiple myeloma cell lines.¹ It is used to study IRE1α action in the endoplasmic reticulum stress response, particularly in the context of cancer.^2,3 It also inhibits phosphatidylinositol kinase in vitro (IC₅₀ = 3.3 µg/ml), but not in cells, and blocks the ribosomal RNA-processing kinase Rio1 (IC₅₀ = ~30 nM).^4,5

1.Ri, M., Tashiro, E., Oikawa, D., et al.Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicingBlood Cancer J.2(7)(2016) 2.Chien, W., Ding, L.W., Sun, Q.Y., et al.Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cellsOncotarget5(13)4881-4894(2014) 3.Sun, H., Lin, D.C., Guo, X., et al.Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemiaOncotarget7(14)18736-18749(2016) 4.Nishioka, H., Sawa, T., Hamada, M., et al.Inhibition of phosphatidylinositol kinase by toyocamycinJ.Antibiot.(Tokyo)43(12)1586-1589(1990) 5.Kiburu, I.N., and LaRonde-LaBlanc, N.Interaction of Rio1 kinase with toyocamycin reveals a conformational switch that controls oligomeric state and catalytic activityPLoS One7(5)(2016)