Survivin is a member of the inhibitor of apoptosis (IAP) protein family and has been implicated in both cell survival and regulation of mitosis in cancer. YM155 is a potent survivin inhibitor with IC50 value of 0.54 nM for survivin promoter activity[2]. YM155 suppressed expression of survivin and induced apoptosis in PC-3 and PPC-1 human hormone-refractory prostate cancer (HRPC) cell lines at 10 nM, but showed little effect on expression levels of other IAP- or Bcl-2-related proteins up to 100 nM. In a s.c. xenografted PC-3 tumor model in mice, 3-day continuous infusions of YM155 at 3 to 10 mg/kg induced massive tumor regression accompanied by suppression of intratumoral surviving and no significant decreases in body weight were observed[2]. Glioma cell lines responded in a dose and time-dependent manner to YM-155 with reduction of cell numbers. U373, LN18, LNZ428, T98G, LN229, and LNZ308 cells exhibited an IC50 of ~ 10-75 nM, while A172 cells were resistant to YM-155 with IC50 ~ 250 nM[3]. Exposure of U373 and LN18 (YM-155 sensitive) glioma cells to 25 nM of YM-155 for 24 h caused a marked loss of mitochondrial membrane potential compared with the control group[3]. Primary effusion lymphoma-patient-derived xenograft mice were treated with YM-155 (5 mg/kg) from days 2-22. The volume of ascites was significantly less in YM155-treated mice than in control mice on day 22 (0.75 mL [median, range 0-2.56 mL] vs. 3.96 mL [median, range 0.7-5.29 mL], p < 0.01)[4].
Sepantronium bromide 细胞实验
Cell Line
Concentration
Treated Time
Description
References
UKF-NB-3
0.49 nM
120 h
YM155 affects the viability of drug-resistant neuroblastoma cells through survivin depletion and p53 activation.
Cell Death Dis. 2016 Oct 13;7(10):e2410.
UKF-NB-6
0.65 nM
120 h
YM155 affects the viability of drug-resistant neuroblastoma cells through survivin depletion and p53 activation.
Cell Death Dis. 2016 Oct 13;7(10):e2410.
CAL27 cells
12.7 nM
24 h
YM155 induced apoptosis in CAL27 cells in a mitochondria and death receptor-dependent manner, and significantly enhanced autophagy, leading to cell death
Cell Death Dis. 2015 May 28;6(5):e1771.
HSC3 cells
19.1 nM
24 h
YM155 induced apoptosis in HSC3 cells in a mitochondria and death receptor-dependent manner, and significantly enhanced autophagy, leading to cell death
Cell Death Dis. 2015 May 28;6(5):e1771.
U251 cells
5 nM
48 h
To evaluate the effects of YM155 on the proliferation and radiosensitivity of U251 cells, the results showed that YM155 reduced cell viability and enhanced radiosensitivity.
J Transl Med. 2018 Mar 23;16(1):79.
U87 cells
5 nM
48 h
To evaluate the effects of YM155 on the proliferation and radiosensitivity of U87 cells, the results showed that YM155 reduced cell viability and enhanced radiosensitivity.
J Transl Med. 2018 Mar 23;16(1):79.
KBM7 cells
100 nM
3 days
To validate the dependency of YM155 on SLC35F2, results showed that cells lacking SLC35F2 were significantly less sensitive to YM155.
Nat Chem Biol. 2014 Sep;10(9):768-773.
Healthy human peripheral blood mononuclear cells (PBMCs)
100 nM
24 h
To evaluate the effect of YM155 on T cell apoptosis, results showed that YM155 increased T cell apoptosis.
Front Immunol. 2021 Aug 6;12:710904.
HeLa cells
25 nM
24 h
The cell viability assay was used to screen the sensitivity of USP32 knockout to YM155, and it was found that USP32 knockout increased sensitivity to YM155.
Theranostics. 2021 Sep 27;11(20):9752-9771.
PC3 cells
10 nM
16 h
To investigate the effect of Sepantronium on oxygen consumption in PC3 cells, the results showed that Sepantronium significantly inhibited oxygen consumption.
Sci Signal. 2015 Aug 11;8(389):ra80.
PC3 cells
10 nM
16 h
To investigate the effect of Sepantronium on ATP production in PC3 cells, the results showed that Sepantronium significantly reduced ATP production.
Sci Signal. 2015 Aug 11;8(389):ra80.
PC3 cells
10 nM
16 h
To investigate the effect of Sepantronium on Complex II activity in PC3 cells, the results showed that Sepantronium significantly inhibited Complex II activity.
Sci Signal. 2015 Aug 11;8(389):ra80.
Sepantronium bromide 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
CAL27 xenograft and transgenic HNSCC mouse models
Intraperitoneal injection
5 mg/kg
Twice per week for 2 weeks
YM155 displayed potent antitumor activities in both CAL27 xenograft and transgenic HNSCC mouse models by delaying tumor onset and suppressing tumor growth
Cell Death Dis. 2015 May 28;6(5):e1771.
Nude mice
Orthotopic glioblastoma model
Intratumoral injection
5 mg/kg
Twice a week, total of five injections
To evaluate the effects of YM155 combined with radiotherapy on the survival and tumor growth in a glioblastoma mouse model, the results showed that combination therapy significantly prolonged survival and inhibited tumor growth.
J Transl Med. 2018 Mar 23;16(1):79.
Mice
SW480 cell xenograft model
Subcutaneous injection
10 mg/kg
Once daily for 7 days
To validate the impact of SLC35F2 expression levels on YM155 efficacy in vivo, results showed that tumors with high SLC35F2 expression were more sensitive to YM155.
Nat Chem Biol. 2014 Sep;10(9):768-773.
Mice
Acute heart transplant rejection model
Intraperitoneal injection
5 mg/kg
Administered on days -1, 1, 3, 5
To evaluate the effect of YM155 on acute heart transplant rejection, results showed that YM155 prolonged graft survival and reduced inflammatory cell infiltration.
Front Immunol. 2021 Aug 6;12:710904.
NOD scid γ (NSG) mice
Breast cancer xenograft model
Intraperitoneal injection
7.5 mg/kg
Twice a week until the end of the experiment
The xenograft model was used to validate the effect of USP32 knockout on the anti-tumor efficacy of YM155, and it was found that USP32 knockout significantly reduced tumor volume and weight.
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