Background:

Toyocamycin is an inhibitor of phosphatidylinositol kinase. It is known as an antifungal antibiotic. [1]

Phosphatidylinositol kinase is one of the important enzymes that take part in the regulation of the pathway of phosphatidylinositol turnover. Phosphatidylinositol turnover is studied to be involved in the cellular response to mitogens and transformation.[1]

Toyocamycin can suppress thapsigargin-, tunicamycin- and 2-deoxyglucose-induced XBP1 mRNA splicing in HeLa cells. This suppression doesn’t affect the activating of transcription factor 6 (ATF6) and PKR-like ER kinase (PERK)’s activation. Toyocamycin prevents IRE1a-induced XBP1 mRNA cleavage in vitro. [2]

In mammalian cells, toyocamycin inhibits RNA synthesis. Toyocamycin induces apoptosis of MM cells including bortezomib-resistant cells at nanomolar levels in a dose-dependent manner. It also inhibited growth of xenografts in an in vivo model of human multiple myeloma. It is also a lead compound for developing anti-MM therapy and XBP1 as an appropriate molecular target for anti-multiple myeloma therapy.[2]

参考文献:
[1]Nishioka H, Sawa T, etal.?, Inhibition of phosphatidylinositol kinase by toyocamycin. J Antibiot (Tokyo). 1990 Dec;43(12):1586-9.
[2]Ri M, Tashiro E, Oikawa D, etal.??, Identification of Toyocamycin,an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. Blood Cancer J. 2012 Jul;2(7):e79.