ym155 survivin inhibitor  (Cayman Chemical)

Journal: APL Bioengineering

Article Title: Survivin modulates stiffness-induced vascular smooth muscle cell motility

doi: 10.1063/5.0252766

Figure Lengend Snippet: Survivin inhibition reduces collective cell migration. VSMCs plated on cell culture plates were treated with various doses of YM155 (c), 10 µg/ml of Mitomycin C (e), or DMSO (a vehicle control). (a) Total cell lysates were collected for immunoblotting. (b) The graphs show the expression of survivin in VSMCs treated with YM155, normalized to that in VSMCs treated with DMSO. n = 5 independent biological replicates. (c) and (e) A scratch-wound assay was performed, and images were captured at 0, 12, and 24 h post-treatment. n = 5–12 independent biological replicates (c) and n = 5 independent biological replicates (e). (d) and (f) Wound closure (%) at 12 and 24 h was calculated using the formula: [(Initial wound size) − (wound size at 12 or 24 h)]/(wound size at 12 or 24 h) × 100. ** p < 0.01, *** p < 0.001; ns, not significant.

Article Snippet: VSMCs were plated on plastic cell culture plates, glass coverslips, or soft and stiff hydrogels in media containing 10% serum with varying doses (0.1, 0.5, 1, or 2 µM) of YM155 (survivin inhibitor; Cat. No. 11490, Cayman Chemical), 10 µg/ml Mitomycin C (proliferation inhibitor; Cat. No. BML-GR311-0002, Enzo Life Sciences), or dimethyl sulfoxide (DMSO; Cat. No. D8418, Sigma-Aldrich) as a vehicle control.

Techniques: Inhibition, Migration, Cell Culture, Control, Western Blot, Expressing, Scratch Wound Assay Assay

Journal: APL Bioengineering

Article Title: Survivin modulates stiffness-induced vascular smooth muscle cell motility

doi: 10.1063/5.0252766

Figure Lengend Snippet: Survivin inhibition decreases single cell migration. (a) VMSCs were sparsely plated on cell culture plates and treated with either YM155 or DMSO for 4 h. Total cell lysates were collected for immunoblotting. (b) The graph shows the expression of survivin in VSMCs treated with varying concentrations of YM155, normalized to that of VSMCs treated with DMSO. n = 4 independent biological replicates. (c)–(e) VSMCs were plated for time-lapse imaging. Manual tracking of these cells was conducted to obtain single-cell trajectories (c) and average cell velocities (d). 49 cells (DMSO), 45 cells (0.1 µM YM155), 42 cells (0.5 µM YM155), 44 cells (1 µM YM155), and 45 cells (2 µM YM155) were analyzed from n = 3 independent biological replicates. (e) Sequences of images from a set of representative time-lapse experiments (arrow-direction of protrusion). * p < 0.05, ** p < 0.01, *** p < 0.001 . ns, not significant.

Article Snippet: VSMCs were plated on plastic cell culture plates, glass coverslips, or soft and stiff hydrogels in media containing 10% serum with varying doses (0.1, 0.5, 1, or 2 µM) of YM155 (survivin inhibitor; Cat. No. 11490, Cayman Chemical), 10 µg/ml Mitomycin C (proliferation inhibitor; Cat. No. BML-GR311-0002, Enzo Life Sciences), or dimethyl sulfoxide (DMSO; Cat. No. D8418, Sigma-Aldrich) as a vehicle control.

Techniques: Inhibition, Migration, Cell Culture, Western Blot, Expressing, Imaging

Journal: APL Bioengineering

Article Title: Survivin modulates stiffness-induced vascular smooth muscle cell motility

doi: 10.1063/5.0252766

Figure Lengend Snippet: Pharmacological inhibition of survivin reduces stiffness-dependent migration. (a) VSMCs were sparsely seeded on fibronectin-coated soft and stiff hydrogels and treated with YM155 or DMSO for 4 h, followed by collection of total lysates for immunoblotting. (b) The graph shows survivin expression in cells treated with varying concentrations of YM155, normalized to the expression in VSMCs on stiff hydrogels treated with DMSO. n = 4 independent biological replicates. (c)–(e) VSMCs were plated for time-lapse video microscopy, and manual tracking of these cells was conducted to obtain single-cell trajectories (c) and average cell velocities (d). 35 cells (soft-DMSO), 36 cells (stiff-DMSO), 38 cells (stiff-0.1 µM YM155), 39 cells (stiff-0.5 µM YM155), 35 cells (stiff-1 µM YM155), and 35 cells (stiff- 2 µM YM155) were analyzed from n = 3 independent biological replicates. (e) Sequences of images from a set of representative time-lapse experiments (arrow-direction of protrusion). * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: VSMCs were plated on plastic cell culture plates, glass coverslips, or soft and stiff hydrogels in media containing 10% serum with varying doses (0.1, 0.5, 1, or 2 µM) of YM155 (survivin inhibitor; Cat. No. 11490, Cayman Chemical), 10 µg/ml Mitomycin C (proliferation inhibitor; Cat. No. BML-GR311-0002, Enzo Life Sciences), or dimethyl sulfoxide (DMSO; Cat. No. D8418, Sigma-Aldrich) as a vehicle control.

Techniques: Inhibition, Migration, Western Blot, Expressing, Microscopy

Journal: APL Bioengineering

Article Title: Survivin modulates stiffness-induced vascular smooth muscle cell motility

doi: 10.1063/5.0252766

Figure Lengend Snippet: Survivin regulates FAK phosphorylation, actin organization, and stress fiber formation. (a) VMSCs were sparsely seeded on fibronectin-coated soft and stiff hydrogels and treated with either YM155 or DMSO. Cells were stained with DAPI, phospho-FAK (Tyr397) antibody and Alexa Fluor 647-phalloidin. Fluorescence images were acquired using a spinning disk confocal microscope with a 63× oil-immersion objective. The outlined boxes indicate the regions shown in the magnified insets. (b) A sum of slices projection of each cell was generated using Fiji/ImageJ, and FAK pY397 clusters were manually counted. 37 cells (soft-DMSO), 44 cells (stiff-DMSO), 33 cells (stiff-0.1 µM YM155), and 37 cells (stiff-2µM YM155) were analyzed from n = 3 independent biological replicates. * p < 0.05, ** p < 0.01.

Article Snippet: VSMCs were plated on plastic cell culture plates, glass coverslips, or soft and stiff hydrogels in media containing 10% serum with varying doses (0.1, 0.5, 1, or 2 µM) of YM155 (survivin inhibitor; Cat. No. 11490, Cayman Chemical), 10 µg/ml Mitomycin C (proliferation inhibitor; Cat. No. BML-GR311-0002, Enzo Life Sciences), or dimethyl sulfoxide (DMSO; Cat. No. D8418, Sigma-Aldrich) as a vehicle control.

Techniques: Phospho-proteomics, Staining, Fluorescence, Microscopy, Generated

Journal: bioRxiv

Article Title: Potency and selectivity of a novel pan-RAS inhibitor in 3D bioprinted organoid tumor models

doi: 10.1101/2025.02.25.640132

Figure Lengend Snippet: (A) Representative high-content fluorescence micrographs of nuclear-stained BOTs generated with KRAS-mutant HCT-116 CRC cells. The panels show the effect of treating BOTs with increasing concentrations (left to right) from 0 nM (vehicle) to 1,000 nM of bortezomib (top), YM155 (middle), and ADT-007 (bottom). All images were acquired for multiple z-planes and resolved into single image using a LionHeart imaging system with a 4X objective after treating BOTs for 72h. Blue: Hoechst 33342 (total nuclei); Green: SYTOX Green (dead cells). Scale bar = 1000 µm. (B) Dose response relationship between drug concentration and total area occupied by cells derived from high-content imaging analysis. As the drug concentration increases, total cell area decreases for all three drugs. Drug potency was calculated based on reduction in area of Hoechst-positive nuclei and normalized to independent untreated controls. Data points represent mean ± SEM from n = 3 independent experiments, each performed in triplicate. Statistical analysis: *p < 0.05, **p < 0.01, ***p < 0.001 in pairwise t-test against control for each drug concentration. (C) Confirmatory dose response from CellTiter-Glo luminescence assay expressed as relative luminescence units (RLU) was obtained in parallel with high-content imaging studies under identical treatment conditions. Data representation and statistical analysis as described above. (D) Dose response curves generated from CellTiter-Glo luminescence data using nonlinear regression in GraphPad Prism. Curves were fitted using four-parameter logistic regression. IC 50 values: ADT-007 = 0.3 nM; bortezomib = 5.8 nM; YM155 = 5.4 nM. *p < 0.01 for ADT-007 vs. bortezomib and YM155.

Article Snippet: Bortezomib (proteasome inhibitor, MW 384.2) and YM155 (survivin inhibitor, MW 443.3) were acquired from Cayman Chemical at 10 mM in DMSO.

Techniques: Fluorescence, Staining, Generated, Mutagenesis, Imaging, Concentration Assay, Derivative Assay, Control, Luminescence Assay

Journal: bioRxiv

Article Title: Potency and selectivity of a novel pan-RAS inhibitor in 3D bioprinted organoid tumor models

doi: 10.1101/2025.02.25.640132

Figure Lengend Snippet: (A) Representative high-content fluorescence micrographs of nuclear-stained BOTs generated with WT RAS HT29 CRC cells. The panels show the effect of treating with increasing concentrations (left to right) from 0 nM (vehicle) to 1,000 nM of bortezomib (top), YM155 (middle), and ADT-007 (bottom). Images acquired using a LionHeart imaging system with a 4X objective after BOTs were treated for 72h. Blue: Hoechst 33342 (total nuclei); Green: SYTOX Green (dead cells). Scale bar = 1000 µm. (B) Dose response relationship between drug concentration and total cell area (Hoescht stain). As drug concentration increases for bortezomib and YM155, blue pixel area decreases, indicating an inhibitory effect on cell proliferation. This effect is not observed with ADT-007, as blue area remains nearly constant along the concentration gradient. Drug efficacy was calculated based on reduction in area of Hoechst-positive nuclei and normalized to independent untreated controls. Data points represent mean ± SEM from n = 3 independent experiments, each performed in triplicate. Statistical analysis: *p < 0.05, **p < 0.01, ***p < 0.001 in pairwise t-test against control for each drug concentration. (C) Confirmatory dose response from CellTiter-Glo luminescence assay expressed as relative luminescence units (RLU) was obtained in parallel with high-content imaging studies under identical treatment conditions. Data representation and statistical analysis as in (B). (D) Dose response curves generated from CellTiter-Glo luminescence data using nonlinear regression in GraphPad Prism. Curves were fitted using four-parameter logistic regression. IC 50 values: ADT-007 >1000 nM; bortezomib = 1.6 nM; YM155 = 7.2 nM. *p < 0.01 for ADT-007 vs. bortezomib and YM155.

Article Snippet: Bortezomib (proteasome inhibitor, MW 384.2) and YM155 (survivin inhibitor, MW 443.3) were acquired from Cayman Chemical at 10 mM in DMSO.

Techniques: Fluorescence, Staining, Generated, Imaging, Concentration Assay, Control, Luminescence Assay

Journal: Cell communication and signaling : CCS

Article Title: Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4 + cells.

doi: 10.1186/s12964-024-01814-4

Figure Lengend Snippet: Fig. 3 Survivin binding within H3K4me3-BvCR is sequence-specific and mobilizes BRG1/SWI complex. A Bar plot of motif enrichment in survivin peaks within and outside of BvCR. MEME motifs enriched within BvCR. Venn diagram of TF identified by DNA sequence motif (MEME suite) and location (ChIP-seq) and mass spectrometry (MS). Group 1 had two unique motifs with different abundances indicated by E-value. B1 Dot plot of enrichment for human proteins/TF within BvCR, by ChIP-seq based ReMap2022 database. B2 Box plot of enrichment for BRG1/SWI complex proteins in ReMap2022 database. Counts underneath protein names indicates the number of overlaps with BvCR. C Coomassie-stained electrophoresis gel depicts survivin-bound proteins precipitated from THP1 cell lysate, separated by molecular weight (MW). Lanes represent two independent experiments (1 and 2, respectively). Bands with BRG1/SWI complex proteins identified by mass spectrometry are indicated by boxes. D Table of BRG1/SWI subunits identified in nuclear material of THP1 cells precipitated by survivin using liquid chromatography mass spectrometry. E Ribbon diagram of the canonical BRG1/SWI complex (PDB ID: 6LTJ) depicts the regions binding survivin (red). Ribbon color corresponds to the normalized fluorescence intensity of survivin binding in the peptide binding array. F Ribbon diagram of protein–protein interaction between the human survivin-H3 tail complex (PDB ID: 3UEF) and ARID1A residues 1722-ARG, 1726-GLU, 1732-LYS, 1738-ASP, 1833-ARG, 1853-GLU, 1855-ILE, and 1862-LYS (F1) and SMARCC2 residues 600-GLU, 643-PRO, 646-ASP, 647-PRO, 650-GLU, 651-ASP, 656-LEU, 682-SER, 683-VAL, 700-PHE, 701-SER, 702-LYS, and 703-MET (F2) in the canonical BRG1/SWI complex (PDB ID: 6LTJ). Survivin, arctic blue; ARID1A, magenta; SMARCC2, rose; interaction residues, yellow

Article Snippet: For RNA-seq, CD4+ cell cultures were treated with recombinant IFNγ (50 ng/ml; Peprotech, Cranbury, NJ, USA) and survivin inhibitor sepantronium bromide (YM155 [32]) (10 nM; Selleck Chemicals, Houston, TX) for 72 h. For qPCR, CD4+ cells were treated with IFNγ, YM155, or JAK-inhibitor tofacitinib (10 μM; Selleck Chemicals) for 48 h.

Techniques: Binding Assay, Sequencing, ChIP-sequencing, Mass Spectrometry, Staining, Electrophoresis, Molecular Weight, Liquid Chromatography, Fluorescence

Journal: iScience

Article Title: Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27.

doi: 10.1016/j.isci.2023.106976

Figure Lengend Snippet: Figure 4. Clustering of peptides based on their atom type abundance, related to Figure S3 The light/dark colors indicate high/low abundance of atom types, respectively. The grayscale bar indicates the logarithm of fluorescence intensity of the peptide in the survivin peptide microarray experiment (black zero intensity, white highest level of intensity). The prediction bar shows the success of the machine learning prediction using the atom type abundance as features (black and cyan colors mark predicted non-interacting and interacting peptides, respectively).

Article Snippet: Cells were treated with survivin inhibitors serpantronium bromide, YM155 22 (YM155, Selleck Chemicals, Houston, TX), as indicated.

Techniques: Peptide Microarray

Journal: iScience

Article Title: Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27.

doi: 10.1016/j.isci.2023.106976

Figure Lengend Snippet: Figure 5. Biolayer interferometry analysis of the survivin-EZH2172-211 peptide interaction, related to Table S9 and Figure S6 (A) BLI experiment showing wavelength shift of biosensors covered by peptide EZH2172-211 upon survivin incubation in the 3.7–100 nM concentration range. The raw data are shown in gray, and the mean posterior predictions are shown in the magenta-cyan color scale corresponding to increasing survivin concentration. (B) Wavelength shift profile from control biosensors (not containing the peptide) for corresponding experiments in (A). The raw data are shown with the magenta-cyan color scale corresponding to increasing survivin concentration. (C) Wavelength shift profile of biosensors covered with survivin upon EZH2172-211 peptide incubation (in concentration range 21.2 nM–21.2 mM). The raw data are shown in gray and the mean posterior predictions are shown in the magenta- cyan color scale corresponding to increasing EZH2172-211 concentration. The wavelength shift profiles were monitored over association (0–900 s) and dissociation (900–2650 s) periods. (D) Wavelength shift profile from control biosensors (not containing survivin) for corresponding experiments in (C). The raw data are shown with the magenta-cyan color scale corresponding to increasing EZH2172-211 concentration.

Article Snippet: Cells were treated with survivin inhibitors serpantronium bromide, YM155 22 (YM155, Selleck Chemicals, Houston, TX), as indicated.

Techniques: Incubation, Concentration Assay, Control

Journal: iScience

Article Title: Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27.

doi: 10.1016/j.isci.2023.106976

Figure Lengend Snippet: Figure 6. NMR titration of survivin with peptides derived from different PRC2 subunits, related to Tables S8 and S10 and Figures S4–S8 (A) Overlay of 2D [15N,1H] NMR spectra of 300 mM [U-15N]-survivin in the absence (cyan) and presence (blue) of 2.3 mM EZH2172–211 peptide measured at 298 K in NMR buffer. Characteristic peaks are annotated. ‘‘sc’’ refers to tryptophan indole resonances. (B) Zoom-in into the NMR-spectra overlay at higher contour lines. Characteristic peaks are annotated. Newly appearing resonances at high peptide concentration are encircled. (C) Intensity changes upon EZH2172–211 interaction were plotted on the survivin structure (PDB: 3UEF; only a single monomer is shown) by the indicated color gradient. The amide moieties are shown as spheres. (D) The ratio of the individual peak intensities in the presence of the EZH2172–211 peptide plotted against the surviving residue number. (E) d1[15N]-1D cross-sections from 2D [15N,1H] NMR spectra of a titration of [U-15N]-survivin in NMR buffer with variable concentrations as indicated of the following peptides: EZH2172–211 (blue), EED128–152 (red), SUZ12573–597 (green), and JARID2170–194 (purple).

Article Snippet: Cells were treated with survivin inhibitors serpantronium bromide, YM155 22 (YM155, Selleck Chemicals, Houston, TX), as indicated.

Techniques: Titration, Derivative Assay, Concentration Assay, Residue

Journal: iScience

Article Title: Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27.

doi: 10.1016/j.isci.2023.106976

Figure Lengend Snippet: Figure 7. Survivin-dependent molecular mechanism of preventing PRC2 from methylating H3K27, related to Table S10 and Figures S9–S11 Histone H3 tails are shown in dark blue and survivin is shown in turquoise. (A) The EZH2 subunit forms a binding pocket to accommodate the survivin molecule. The EZH2 binding pocket is shown in the surface representation. (B) Survivin directly interacts with the catalytic SET domain of the EZH2 subunit and may disrupt the enzymatic activity required for trimethylation of H3K27.

Article Snippet: Cells were treated with survivin inhibitors serpantronium bromide, YM155 22 (YM155, Selleck Chemicals, Houston, TX), as indicated.

Techniques: Binding Assay, Activity Assay

Journal: Frontiers in Pharmacology

Article Title: Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension

doi: 10.3389/fphar.2023.1145994

Figure Lengend Snippet: Schematic of the experimental design. Vehicle: DMSO; SU5416: Sugen; YM155: Survivin inhibitor.

Article Snippet: In the groups treated with the survivin inhibitor, 5 mg/kg of YM155 (CAS 781661-94-7, Calbiochem), resuspended in saline solution, was administrated subcutaneously every day during the last week of SU5416/hypoxia exposure ( ).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension

doi: 10.3389/fphar.2023.1145994

Figure Lengend Snippet: Effect of YM155 on survivin protein expression in small pulmonary arteries in SU5416/hypoxia-induced PAH mice. (A) Photomicrographs showing the immunostaining for survivin in small pulmonary vessels in the different experimental groups (Veh-Nx = vehicle and normoxia; YM155-Nx = vehicle, normoxia and YM155; SU-Hx = SU5416 and hypoxia; SU-Hx-YM155 = SU5416, hypoxia and YM155). (B) Percent of survivin positive vessels with respect to the total number of vessels in each experimental group. Values are expressed as mean ± SD. Statistical significance was assessed by the one-way ANOVA. Arrows indicate the localization of survivin in small pulmonary arteries.

Article Snippet: In the groups treated with the survivin inhibitor, 5 mg/kg of YM155 (CAS 781661-94-7, Calbiochem), resuspended in saline solution, was administrated subcutaneously every day during the last week of SU5416/hypoxia exposure ( ).

Techniques: Expressing, Immunostaining

Journal: Frontiers in Pharmacology

Article Title: Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension

doi: 10.3389/fphar.2023.1145994

Figure Lengend Snippet: Effect of YM155 on survivin protein and mRNA expression in whole lung extracts of SU5416/hypoxia-induced PAH mice. (A) Immunoblots of the expression of survivin and the constititutive protein ß -actin in the different experimental groups (Veh-Nx = vehicle and normoxia; YM155-Nx = vehicle, normoxia and YM155; SU-Hx = SU5416 and hypoxia; SU-Hx-YM155 = SU5416, hypoxia and YM155). (B) Quantitative mRNA expression of BIRC5, the gene encoding survivin, related to Actb expression using RT-PCR in the different experimental groups. Values are expressed as median (IQR) and statistical significance was assessed by the Kruskal–Wallis test.

Article Snippet: In the groups treated with the survivin inhibitor, 5 mg/kg of YM155 (CAS 781661-94-7, Calbiochem), resuspended in saline solution, was administrated subcutaneously every day during the last week of SU5416/hypoxia exposure ( ).

Techniques: Expressing, Western Blot, Reverse Transcription Polymerase Chain Reaction