Toyocamycin (Vengicide) is an adenosine analog produced by Streptomyces diastatochromogenes, acts as an XBP1 inhibitor. Toyocamycin blocks RNA synthesis and ribosome function, and induces apoptosis. Toyocamycin affects IRE1α-XBP1 pathway, and inhibits XBP1 mRNA cleavage with an IC50 value of 80 nM with affecting IRE1α auto-phosphorylation. Toyocamycin specifically inhibits CDK9 with an IC50 value of 79 nM[2].IC50 & Target:IC50: 80 nM (XBP1 activation); 79 nM (CDK9); 2.8 μM (CDK7); 0.67 μM (CDK2), 15 μM (CDK4), >10 μM (CDK6)[2]In Vitro: Toyocamycin (0-0.3 μM; 4 h) inhibits ER stress-induced XBP1 mRNA splicing, and selectively inhibits the ER stress-induced activation of the IRE1α-XBP1 pathway.
Toyocamycin (0-0.3 μM; 24 h) inhibits constitutive activation of XBP1 in MM cell lines.
Toyocamycin (250 nM; 48 h) inhibits CDK9 enzymatic activity in colon cancer cell lines[2].
Toyocamycin (0.05 nM-50 μM; 48 h and 72 h) doesn’t trigger immediate cytotoxicity against YB5 and HCT116 cells with cell viability above 50%, but results eradication of cancer cells 2 weeks later at 10 nM for 24 h treatment[2].
Toyocamycin?(0-100 nM; 24 or 48 h) induces?apoptosis?via mitochondrial pathway in PC-3 cells.
Toyocamycin (60 nM; 0-48 h) promotes p38/ERK MAPK activation and regulates ROS-mediated apoptosis by inhibition of p38 on?ERK?MAPK.
In Vivo: Toyocamycin (0.5 mg/kg, 1.0 mg/kg; i.p.; twice a week; 2 weeks) shows anti-tumor activity in a xenograft model with human multiple myeloma (MM) cells, while the anti-tumor effect enhanced by Bortezomib (HY-10227).