YM155

Validation & Quality Control

Product Citations(11)

Proc Natl Acad Sci U S A, 2012, 109(2):600-5

Leukemia, 2012, 26(4), 623-632

Basic Res Cardiol, 2011, 106(6), 1207-1220

Cell Death Dis, 2013, 4, e471

Mol Cancer Ther, 2012, 11(9):1988-98
Int J Biochem Cell Biol, 2012, 44(1), 158-169

PLoS One, 2011, 6(8), e21980

BMC Cancer, 2012, 12, 619

Pediatr Blood Cancer, 2013, 60(1):35-40

Anticancer Res, 2012, 32(5):1681-8
Adv Biosci Biotechnol, 2012, 3(6A):657-664

Customer Reviews(11) in vivo invitation

Survivin down-regulation sensitizes ABT-263-induced apoptosis in HCC cells. A. LH86 cells were treated as indicated and cell lysates were prepared for Western blotting. Pro-apoptotic proteins: Bax, Bad, and Bak and anti-apoptotic proteins Bcl-xL and Mcl-1 were assessed with specific antibodies respectively. b-actin was detected and served as an equal protein loading control. B. LH86 cells were untreated or treated with ABT-263 (1 μM), YM-155 (1 μM) or combination of ABT-263 (1 μM) and YM155 (1 μM) for up to 6 h as indicated. Then cells were harvested and cell lysates were prepared for Western blotting. Anti-survivin and anti-Bcl-xL polyclonal antibodies were used to assess protein levels for survivin and Bcl-xL respectively. b-actin was used as an equal protein loading control. The band intensities of survivin, Bcl-xL, and b-actin was qualified with Image J software. C. LH86 cells were transiently transfected with synthesized random siRNA (control) or survivin specific siRNA duplexes, and 48 h posttransfection, cells were subjected to Western blotting analysis with anti-survivin polyclonal antibody. β-actin was used as an equal protein loading control. D. LH86 cells were transfected with synthesized random control siRNA or survivin specific siRNA, and 48 h post-transfection, cells were untreated or treated with ABT-263 (1 μM) for 24 h and then subjected to Hoechst staining to show apoptotic cells with condensed nuclei (representative apoptotic cells were marked with white arrows). E. LH86 cells were treated as in Figure 4D and apoptosis was measured as in Figure 2A. Statistical analysis was performed for apoptosis ratio by counting the number of cells with apoptotic nuclei (*p<0.05). F. LH86 cells treated as in Figure 4D were harvested and cell lysates were prepared and subjected to Western blotting. Apoptosis was determined through caspase 3 activation. β-actin was used as an equal protein loading control.

PLoS ONE , 2011, 6, e21980. YM155 purchased from Selleck

Quality Control & MSDS

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YM155 is available in the following compound libraries:

Inhibitor Library (96-well) Chemical Library (96-well) Cambridge Cancer Compound Library(96-well)

Product Information

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Cat.No. Product Name Solubility (25°C)

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S1130 YM155 89 mg/mL 55 mg/mL 6 mg/mL
Research Area
Research Area
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1130	YM155	89 mg/mL	55 mg/mL	6 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	YM155 is a potent IAP (inhibitor of apoptosis proteins) inhibitor for survivin with IC50 of 0.54 nM.
Targets	Survivin
IC50	0.54 nM ^[1]
In vitro	YM155 is not sensitive to survivn gene promoter-driven luciferase reporter activity even at 30 μM. YM155 significantly inhibits endogenous survivin expression in PC-3 and PPC-1 human HRPC cells with deficient p53 through transcriptional inhibition of the survivin gene promoter. On the contrary YM155 shows no sufficient effect on protein expression of c-IAP2, XIAP, Bcl-2, Bcl-xL, Bad, α-actin, and β-tubulin at 100 nM. YM155 indicates great apoptosis in human cancer cell lines including PC-3 and PPC-1 with a concomitant increase in caspase-3 activity. YM155 potently inhibits human cancer cell lines (mutated or truncated p53) including PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5 and A375 with IC50 from 2.3 to 11 nM, respectively. ^[1] YM155 increases the sensitivity of NSCLC cells to γ-radiation. The combination of YM155 and γ-radiation increases both the number of apoptotic cells and the activity of caspase-3. YM155 delays the repair of radiation-induced double-strand breaks in nuclear DNA. ^[2]
In vivo	YM155 completely inhibits the tumor growth of PC-3 s.c. xenografted prostate tumors at doses of 3 and 10 mg/kg, without body weight loss and blood cell count decrease. Pharmacokinetic analysis shows that YM155 is highly distributed to tumor tissue. Moreover, YM155 shows 80% TGI at a dose of 5 mg/kg in PC-3 orthotopic xenografts. ^[1] The combination therapy with YM155 and γ-radiation shows great antitumor activity against H460 or Calu6 xenografts in nude mice. ^[2]
Clinical Trials	YM155 is currently in Phase II clinical trial in advanced non-small cell lung carcinoma.
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

Promoter-luciferase reporter assay	A 2,767-bp sequence of human survivin gene promoter is isolated from human genomic DNA by PCR using Pyrobest polymerase and the following primers: 5'-GCGCGCTCGAGTCTAGACATGCGGATATATTC-3' and 5'-GCGCGAA-GCTTTGGCGGTTAATGGCGCGC-3'. The resulting PCR fragment is digested with XhoI/HindIII and ligated into the XhoI/HindIII cleavage site of the pGL3-Basic vector. The resulting plasmid is named pSUR-luc. DNA sequencing is done on all amplified sequences by a DNA sequencer. The activity of pSUR-luc is confirmed by luciferase assay with transiently transfected HeLa-S3 cells. Luciferase assay is done. The pGL3 control vector, which contains the SV40 promoter and enhancer sequences, is used. HeLa cells are stably transfected with pSUR-luc and pSV2bsr by Lipofect-AMINE 2000. After blasticidin selection at 10 μg/mL, a single colony is chosen based on appropriate luciferase signals and genetic stability over time and named HeLa-SURP-luc. CHO cells are stably transfected with pGL3-control and pSV2bsr. After blasticidin selection at 10 μg/mL, a single colony is chosen based on appropriate luciferase signals and genetic stability over time and named CHO-SV40-luc. Stocked cells from the HeLa-SURP-luc and CHO-SV40-luc clones are used for chemical screening and characterization of YM155. YM155 in DMSO are added to the cells, which had been seeded the previous day on 96-well plastic plates at 5 × 10³ per well. Luciferase activity is measured 24 hours later. IC50 is calculated by logistic analysis.

Promoter-luciferase reporter assay

A 2,767-bp sequence of human survivin gene promoter is isolated from human genomic DNA by PCR using Pyrobest polymerase and the following primers: 5'-GCGCGCTCGAGTCTAGACATGCGGATATATTC-3' and 5'-GCGCGAA-GCTTTGGCGGTTAATGGCGCGC-3'. The resulting PCR fragment is digested with XhoI/HindIII and ligated into the XhoI/HindIII cleavage site of the pGL3-Basic vector. The resulting plasmid is named pSUR-luc. DNA sequencing is done on all amplified sequences by a DNA sequencer. The activity of pSUR-luc is confirmed by luciferase assay with transiently transfected HeLa-S3 cells. Luciferase assay is done. The pGL3 control vector, which contains the SV40 promoter and enhancer sequences, is used. HeLa cells are stably transfected with pSUR-luc and pSV2bsr by Lipofect-AMINE 2000. After blasticidin selection at 10 μg/mL, a single colony is chosen based on appropriate luciferase signals and genetic stability over time and named HeLa-SURP-luc. CHO cells are stably transfected with pGL3-control and pSV2bsr. After blasticidin selection at 10 μg/mL, a single colony is chosen based on appropriate luciferase signals and genetic stability over time and named CHO-SV40-luc. Stocked cells from the HeLa-SURP-luc and CHO-SV40-luc clones are used for chemical screening and characterization of YM155. YM155 in DMSO are added to the cells, which had been seeded the previous day on 96-well plastic plates at 5 × 10³ per well. Luciferase activity is measured 24 hours later. IC50 is calculated by logistic analysis.

Cell Assay: ^[1]

Cell lines	Hormone refractory prostate cancer cell lines (PC-3, PPC-1, DU145, TSU-Pr1 and 22Rv1) and malignant melanoma cell lines (SK-MEL-5 and A375)
Concentrations	~ 100 nM
Incubation Time	48 hours
Method	Cells are seeded in 96-well plates at a density of 5-40 × 10³. YM155 is dissolved in DMSO and added to cells for 48 hours. Then the cell count is determined by sulforhodamine B assay.

Animal Study: ^[1]

Animal Models	PC-3 s.c. (orthotopic) xenografts in male nude mice (BALB/c nu/nu)
Formulation	Dissolved and diluted in saline immediately before administration
Dosages	5 mg/kg
Administration	Subcutaneous injection as a 3-day continuous infusion per week for 3 weeks by an implanted micro-osmotic pump

1

References

Chemical Information

Download YM155 SDF

Molecular Weight (MW)	443.29
Formula	C₂₀H₁₉BrN₄O₃
CAS No.	781661-94-7, 753440-91-4 (FREE BASE)
Synonyms	N/A

Solubility (25°C) DMSO 55 mg/mL Water 89 mg/mL Ethanol 6 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	1H-Naphth[2,3-d]imidazolium, 4,9-dihydro-1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(2-pyrazinylmethyl)-, bromide (1:1)

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Research Area

Customer Reviews (11)

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Rating

Source

Basic Res Cardiol, 2011, 106(6), 1207-1220. YM155 purchased from Selleck

Method

Western blot analysis, TUNEL assay, Immunostaining for survivin protein

Cell Lines

Neonatal rat cardiomyocytes

Concentrations

5 mg/kg/day

Incubation Time

5 d

Results

After the animals were pretreated with YM155 (5 mg/kg/day) for 5 days, the level of survivin decreased to 80, 78 and 52% of the baseline expression in non-injury, sham burn or burn injury hearts (Fig. a, top panel, and b, left panel). The basal cleaved caspase-3 level was almost undetectable, whereas after injection of YM155 for 5 days, the expression was signiﬁcantly elevated to 6.5-fold (Fig. a, middle panel, and b, right panel). After 6 h of burn injury, the level of cleaved caspase-3 increased to 9.0-fold. Furthermore, in the normal or sham rats, there were no apoptotic staining in the hearts examined (Fig. c). When animals were pretreated with YM155, the apoptotic staining was signiﬁcantly increased, particularly after the burn (0.61 ± 0.25% in normal group, 0.72 ± 0.17% in sham group, 2.18 ± 0.43% in YM155 group) (Fig. d), suggesting that the survivin is an important anti-apoptotic regulator of cardiomyocytes after burn injury.

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Rating

Source

Anticancer Res, 2012, 32(5), 1681-8. YM155 purchased from Selleck

Method

Immunoblot analysis/Cell cycle analysis/cytotoxicity assay

Cell Lines

MiaPaCa2 cell line

Concentrations

2-16 nM

Incubation Time

Results

YM155 induced cell death in a dose-dependent manner(Figure A); however, marked cell cycle arrest was not noted, merely an increased proportion of cells in the subG1 fraction. and a decrease in the G1 fraction (Figure B). YM155 treatment successfully suppressed the mRNA and the protein expression of survivin, as confirmed by RT-PCR and westernblot analysis (Figure C and D). In addition, the cleavage of PARP increased in accordance with the increase in the proportion of dead cells induced by YM155 (Figure D).

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Rating

Source

Adv Biosci Biotechnol, 2012, 3(6A), 657-664. YM155 purchased from Selleck

Method

Apoptosis assay

Cell Lines

IPF fibroblasts

Concentrations

10 µM

Incubation Time

16 h

Results

There was strong correlation between apoptosis induced by Fas-activation with YM155 and Fas-activation with CAY1062.

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Rating

Source

Proc Natl Acad Sci U S A, 2012, 109(2), 600-5. YM155 purchased from Selleck

Method

Western blotting

Cell Lines

HELF

Concentrations

0-0.5 Nm

Incubation Time

9 h

Results

VZV titers decreased in the presence of YM155- compared with DMSO-treated HELF at 48 hpi (Fig. 7A ). VZV spread in YM155-treated HELF was also much more restricted compared with DMSO-treated HELF (Fig. B); mean plaque sizes were ∼0.2 mm2with YM155 compared with∼0.4 mm2with DMSO. Impaired VZV replication in the absence of survivin was furthercon firmed by decreased expression of VZV proteins IE62, ORF4, and ORF11 at 24 hpi in the presence of increasing concentrations of the survivin inhibitor (Fig. C).

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Rating

Source

PLoS ONE , 2011, 6, e21980. YM155 purchased from Selleck

Method

Hoechst staining, Western blotting, Cell colony formation assays

Cell Lines

LH86 cells, Huh7 cells

Concentrations

1 µM

Incubation Time

6 h

Results

As shown in Figure A, B, C, D, E and F, neither ABT-263(1 µM) nor YM-155(1 µM) single treatment was able to induce apoptotic events in HCC cells. Surprisingly, a combination treatment of ABT-263 (1 µM) with YM-155 (1 µM) induced dramatic apoptosis within 6 h. Additional experiments were done to determine the anti-tumor activities of combination of ABT-263 and YM-155 inhibition when analyzed by in vitro colony formation assays. As shown in Figure G and F, median dose of ABT-263 and YM-155 combination treatment significantly reduced HCC cell proliferation. These results suggest that survivin inhibitor YM-155 can sensitize ABT-263 to induce apoptosis in HCC cells.

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Rating

Source

PLoS ONE , 2011, 6, e21980. YM155 purchased from Selleck

Method

Western blotting, Hoechst staining

Cell Lines

LH86 cells

Concentrations

1 µM

Incubation Time

6 h

Results

As shown in Figure A, the combination treatment of HCC cells with ABT-263 (1 µM) and YM-155 (1 µM) for up to 6 h has no effects on the expressions of either anti-apoptotic protein Bcl-xL or pro-apoptotic proteins including Bad, Bak, and Bax. However, as expected, the presence of YM-155 significantly decreased survivin protein expression (Figure B, left third lane). Co-treatment of cells with ABT-263 (1 µM) and YM-155 (1 µM) induced an even greater decrease in survivin protein expression (Figure B, right two lanes) than that of YM-155 itself did. However, we indeed observed that ABT-263 single treatment for 3 h resulted in survivin increase (Figure B). To further determine survivin inhibition plays a critical role in sensitizing ABT-263 to induce apoptosis in HCC cells, we down-regulated survivin expression in HCC cells by siRNA duplexes targeted against human survivin mRNA, and then examined the expression of survivin by Western blotting (Figure C) and apoptotic events after ABT-263 treatments. The results demonstrated that ABT-263 induced significant apoptosis in the survivin siRNA-transfected cells, but not in siRNA Random-transfected (control) cells (Figure D, E, and F).

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Rating

Source

Basic Res Cardiol, 2011, 106(6), 1207-1220. YM155 purchased from Selleck

Method

Cell Death Detection, ELISA, Western blot analysis

Cell Lines

Neonatal rat cardiomyocytes

Concentrations

3–300 nM

Incubation Time

0-12 h

Results

"As shown in Fig. a, Burn serum increased the optical density in neonatal rat cardiomyocytes from 0.21 ± 0.01 to 1.10 ± 0.11. YM155 could further enhanced burn serum-induced apoptosis in a concentration-dependent manner, with a signiﬁcant cell apoptosis effect detectable at 100 nM, and a more pronounced effect at 300 nM. Therefore, in all subsequent experiments in vitro, we used 100 nM YM155 to inhibit survivin expression. From Fig. b, the apoptosis induced by burn serum was increased by YM155, not only at 2 h, but also at 12 h. Furthermore, when cardiomyocytes were pre-incubated with YM155 2 h prior burn serum stimulation, the levels of cleaved caspase-3 were signiﬁcantly greater than those from cells pretreated with vehicle (Fig. c, middle panel, and d, right panel).

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Rating

Source

Leukemia , 2012, 26(4), 623-632. YM155 purchased from Selleck

Method

MTS assay

Cell Lines

REH/RCH/SUPB15/HAL01 cell lines

Concentrations

0-10000 nM

Incubation Time

72 h

Results

Each of the cell lines tested showed a dose-dependent sensitivity to YM155 as measured by cell viability 72 h after exposure

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Rating

Source

Leukemia, 2012, 26(4), 623-632. YM155 purchased from Selleck

Method

Small interfering RNA knockdown

Cell Lines

SUPB15 cells

Concentrations

100 nM

Incubation Time

96 h

Results

Knock-down of p53 did not rescue the effects on cell viability of either imatinib or ABL siRNA. In contrast, silencing of p53 did rescue the effects of both survivin siRNA and YM155.

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Rating

Source

Lihua Min of Chinese Academy of Sciences. YM155 purchased from Selleck

Method

qRT-PCR

Cell Lines

liver cell

Concentrations

Incubation Time

48 h

Results

Total RNA from livers of these mice were isolated from tissues using TRIZOL (Invitrogen). cDNA synthesis was performed with the M-MLV RTase cDNA Synthesis Kit (Promega). qRT-PCR reactions were performed using SYBR Green (Takara) on ABI 7500 Fast system. Expression levels of Survivin gene were measured by qRT-PCR in livers injected with 0.9% Nacl (91#,92#) or YM155 48 hours after DEN treatment.

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Rating

Source

Dr Chunrong Yu of RoswelI Park Cancer Institute. YM155 purchased from Selleck

Method

Western blotting

Cell Lines

U-251 cell line, PC-3 cell line

Concentrations

0-100 nM

Incubation Time

Results

Product Citations (11)

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis. [Sen N, et al. Proc Natl Acad Sci U S A 2012;109(2):600-5]
PubMed: 22190485
Targeting survivin and p53 in pediatric acute lymphoblastic leukemia. [Tyner JW, et al. Leukemia 2012;26(4), 623-632]
PubMed: 21960246
Burn-induced apoptosis of cardiomyocytes is survivin dependent and regulated by PI3K/Akt, p38 MAPK and ERK pathways. [Cao W, et al. Basic Res Cardiol 2011;106(6), 1207-1220]
PubMed: 21706383

Salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis through DR5 and survivin-dependent mechanisms. [Charette N, et al. Cell Death Dis 2013;4, e471]
PubMed: 23348585
YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels. [Kumar B, et al. Mol Cancer Ther 2012;11(9):1988-98]
PubMed: 22723337
Survivin expression induced by endothelin-1 promotes myofibroblast resistance to apoptosis. [Horowitz JC, et al. Int J Biochem Cell Biol 2012;44(1), 158-169]
PubMed: 22041029
Survivin inhibition is critical for Bcl-2 inhibitor-induced apoptosis in hepatocellular carcinoma cells. [Zhao X, et al. PLoS One 2011;6(8), e21980]
PubMed: 21829603
Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells. [Tao YF, et al. BMC Cancer 2012;12, 619]
PubMed: 23267699
BIRC5 expression is a poor prognostic marker in Ewing sarcoma. [Hingorani P, et al. Pediatr Blood Cancer 2013;60(1):35-40]
PubMed: 22961763
The Survivin Suppressant YM155 Potentiates Chemosensitivity to Gemcitabine in the Human Pancreatic Cancer Cell Line MiaPaCa-2. [Yoon DH, et al. Anticancer Res 2012;32(5):1681-8]
PubMed: 22593446
Increased survivin expression contributes to apoptosis-resistance in IPF fibroblasts. [Sisson TH, et al. Adv Biosci Biotechnol 2012;3(6A):657-664]
PubMed: 23355956

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3Monday–Friday 9:00 AM–5:00 PM (Central Time)

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Validation & Quality Control

Product Citations(11)

Customer Reviews(11) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

YM155 is available in the following compound libraries:

Product Information

Compare Survivin Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[1]

References

Chemical Information

Research Area

Customer Reviews (11)

Product Citations (11)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related Survivin Inhibitors

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Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1130	YM155	89 mg/mL	55 mg/mL	6 mg/mL

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YM155

Validation & Quality Control

Product Citations(11)

Customer Reviews(11) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

YM155 is available in the following compound libraries:

Product Information

Compare Survivin Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [1]

Animal Study: [1]

References

Chemical Information

Research Area

Customer Reviews (11)

Product Citations (11)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related Survivin Inhibitors

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Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[1]