Toyocamycin is an adenosine analogue produced by Streptomyces diastatochromogenes and can be used as an XBP1 inhibitor.Toyocamycin blocks RNA synthesis and ribosomal function and induces apoptosis.Toyocamycin affects the IRE1α-XBP1 pathway and inhibits XBP1 mRNA. Toyocamycin affects the IRE1α-XBP1 pathway and inhibits the cleavage of XBP1 mRNA with an IC50 value of 80 nM, and also affects the autophosphorylation of IRE1α. Toyocamycin specifically inhibits CDK9 with an IC50 value of 79 nM[1][2][3] .Toyocamycin (0-0.3 μM; 4 h) inhibits ER stress-induced XBP1 mRNA splicing and selectively inhibits ER stress-induced activation of the IRE1α-XBP1 pathway[1][2][3].Toyocamycin inhibits the constitutive activation of XBP1 in MM cell lines at concentrations of 0-0.3 μM for 24 h[1] .Toyocamycin inhibited the enzymatic activity of CDK9 in colon cancer cell lines at a concentration of 250 nM for 48 hours. In contrast, at concentrations ranging from 0.05 nM to 50 μM for 48 and 72 hours, Toyocamycin did not cause immediate cytotoxicity in YB5 and HCT116 cells with cell viability greater than 50%, but resulted in eradication of the cancer cells after 2 weeks following a 10 nM treatment for 24 hours[2] .Toyocamycin induces apoptosis in PC-3 cells via the mitochondrial pathway at concentrations ranging from 0-100 nM for 24 or 48 hours[3] .At 60 nM for 0-48 h, Toyocamycin promotes p38/ERK MAPK activation and regulates ROS-mediated apoptosis by inhibiting p38 on ERK MAPK[3] .
Toyocamycin/丰加霉素 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT116 cells
250 nM
24 hours
Induced GFP expression and caused gene expression changes
Cancers (Basel). 2022 Jul 8;14(14):3340
HeLa/XBP1-luc cells
0.08 µM
24 hours
Inhibition of thapsigargin-induced XBP1-luciferase activation
Blood Cancer J. 2012 Jul;2(7):e79
Mature mouse oligodendrocytes (mOLs)
0.05 µM
24 hours
To evaluate the effect of Toyocamycin on the survival of mature oligodendrocytes. Results showed a dose-dependent decrease in the viability of mOLs treated with Toyocamycin.
Glia. 2021 Feb;69(2):424-435
HEK293T cells
10 µM
24 hours
Test the inhibitory effect of Toyocamycin on ribozyme self-cleavage
RNA. 2006 May;12(5):797-806
Saccharomyces cerevisiae W303-1A
2.8-70 µM
24 hours
Assess the growth inhibitory effect of TM on S. cerevisiae expressing CaCNT.
Microbiol Spectr. 2022 Aug 31;10(4):e0113822
Candida albicans SC5314
1.25-10 µM
24 hours
Evaluate the growth inhibitory effect of TM on C. albicans, with an estimated IC50 between 1.25-2.5 μM.
Microbiol Spectr. 2022 Aug 31;10(4):e0113822
L cells
0.3 µg/ml
2-8 hours
Toyocamycin treatment caused the gradual disappearance of the fibrillar zones of nucleoli, resulting in a homogeneous granular appearance.
J Cell Biol. 1971 Jun;49(3):803-15
KB cells
0.3 µg/ml
2-8 hours
Toyocamycin treatment caused the gradual disappearance of the fibrillar zones of nucleoli, resulting in a homogeneous granular appearance.
J Cell Biol. 1971 Jun;49(3):803-15
HeLa cells
0.18 µM
4 hours
Inhibition of thapsigargin-induced endogenous XBP1 mRNA splicing
Blood Cancer J. 2012 Jul;2(7):e79
S2 cells
100 nM
48 hours
Toyocamycin significantly inhibited the relative cell viability and colony-forming ability of IPW-low DCIS cells
Breast Cancer Res. 2022 Jan 25;24(1):6
HEK79 cells
1 µM
48 hours
Inhibit ribozyme self-cleavage and induce luciferase expression
RNA. 2006 May;12(5):797-806
RPMI8226 cells
0.1 µM
6 hours
Reduction in the levels of spliced-XBP1
Blood Cancer J. 2012 Jul;2(7):e79
SUM225 cells
100 nM
48 hours
Toyocamycin significantly inhibited the relative cell viability and colony-forming ability of IPW-low DCIS cells
Breast Cancer Res. 2022 Jan 25;24(1):6
DCIS.com cells
100 nM
48 hours
Toyocamycin significantly inhibited the relative cell viability and colony-forming ability of IPW-low DCIS cells
Breast Cancer Res. 2022 Jan 25;24(1):6
YB5 cells
5 µM
72 hours
Induced GFP expression, with over 60% of YB5 cells expressing GFP
Cancers (Basel). 2022 Jul 8;14(14):3340
Mouse oligodendrocyte progenitor cells (mOPCs)
0.05 µM
8 hours
To investigate the inhibitory effect of Toyocamycin on Xbp1 splicing and its impact on ERSR. Results showed that Toyocamycin reduced transcript levels of Xbp1s and its downstream targets ERdj4 and Edem, while upregulating pro-apoptotic ISR genes Chop and Gadd34.
Glia. 2021 Feb;69(2):424-435
Toyocamycin/丰加霉素 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SCID mice
Human multiple myeloma xenograft model
Intraperitoneal injection
0.5 mg/kg or 1.0 mg/kg
Twice weekly or once weekly for 2 weeks
Evaluation of anti-tumor activity of toyocamycin in a human multiple myeloma xenograft model
Blood Cancer J. 2012 Jul;2(7):e79
Nude mice
DCIS.com cell implantation model
Intraperitoneal injection
2 mg/kg
Once a week until the experimental endpoint
Toyocamycin significantly suppressed the tumor growth of DCIS.com cells in vivo
Validate the inhibitory effect of Toyocamycin and FUR combination on ribozyme self-cleavage in vivo
RNA. 2006 May;12(5):797-806
Toyocamycin/丰加霉素 动物研究
Animal study
Administered intravenously at doses of 0.5 mg/kg and 1.0 mg/kg twice weekly for 2 weeks, Toyocamycin showed antitumour activity in a human multiple myeloma (MM) cell xenograft model, which was potentiated by the combination of Bortezomib[1].
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