cb 839  (MedChemExpress)

Journal: iScience

Article Title: RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells

doi: 10.1016/j.isci.2026.115236

Figure Lengend Snippet: Pharmacological inhibition of RUVBL1/2 ATPase activity in NB cell lines (A) Violin plots comparing DepMap RUVBL1 and RUVBL2 dependency scores from 34 NB cell lines to sets of essential and non-essential genes. ∗∗∗∗ p value <0.0001, two-sided Wilcoxon rank-sum test. (B) Western blot showing transient siRNA-mediated knockdown of RUVBL1 and RUVBL2 after 3 days of transfection. Scrambled siRNA was used as control (siCtrl). (C) Time-dependent effect of siRNA-mediated knockdown of RUVBL1 and/or RUVBL2 on NB cell line proliferation, as monitored by live scanning for cell confluency at regular time intervals with IncuCyte S3 system. Cell growth was normalized relative to the first scan at time zero. Results are mean ± SEM of 3 independent biological replicates. (D) Cell viability dose dependency curves after treatment with the RUVBL1/2 inhibitor CB-6644 in 7 different NB cell lines, as indicated. Mean IC50 values are indicated for each cell line (2–6 biological replicates). Cell viability was determined by resazurin assay. (E) Time-dependent effect of CB-6644 (250 nM or 500 nM) treatment on NB cell line proliferation, monitored as in C. (F) Long-term (14 days) effect of CB-6644 (250 nM) on NB cell growth. Cells were stained with crystal violet. See for western blot source data.

Article Snippet: CB-6644 , MedChemExpress , Cat# HY-114429.

Techniques: Inhibition, Activity Assay, Western Blot, Knockdown, Transfection, Control, Resazurin Assay, Staining

Journal: iScience

Article Title: RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells

doi: 10.1016/j.isci.2026.115236

Figure Lengend Snippet: Transcriptomic response to CB-6644 treatment of NB cells CLB-BAR and SK-N-AS NB cells were treated for 72 h with CB-6644 250 nM and differential gene expression (DGE) was determined. (A) Volcano plot for both cell lines as indicated. Differentially expressed genes (threshold log2FoldChange of ±1 at 1% FDR) indicated in blue with top up/downregulated and genes discussed in main text labeled. p values calculated using the Wald Statistic, as implemented in the DESeq2 package. (B) GSEA running score plots for 2 Hallmark gene sets in CLB-BAR cells as indicated. p values calculated using a permutation test as implemented in the fgsea package. (C) GSEA results with heatmap comparing normalized enrichment values (NES, color key) for both cell lines after treatment with CB-6644 (CB; 250 nM) and elimusertib (Eli; 50 nM) as indicated. Gene sets that were not significant (Padj <0.05) were left blank. Columns (gene sets) were hierarchically clustered as indicated in dendrogram. See for detailed DGE and GSEA results.

Article Snippet: CB-6644 , MedChemExpress , Cat# HY-114429.

Techniques: Gene Expression, Labeling

Journal: iScience

Article Title: RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells

doi: 10.1016/j.isci.2026.115236

Figure Lengend Snippet: Experimental validation of transcriptomic responses upon CB-6644 treatment of NB cells Western blots showing the effect of different CB-6644 (250 nM) treatment duration on (phospho-) protein expression in 4 NB cell lines as indicated. N/C-MYC denotes MYCN for CLB-BA, CLB-GA, and NB1, and MYC for SK-N-AS and were detected by two independent antibodies. Cl, cleaved. See for western blot source data.

Article Snippet: CB-6644 , MedChemExpress , Cat# HY-114429.

Techniques: Biomarker Discovery, Western Blot, Expressing

Journal: iScience

Article Title: RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells

doi: 10.1016/j.isci.2026.115236

Figure Lengend Snippet: RUVBL2 and MYCN CUT&RUN results in CLB-BAR NB cells (A) MYCN (top, blue) and RUVBL2 (bottom, gray) CUT&RUN peaks at the RUVBL2 , MYCN , and MYC gene location in CLB-BAR cells, as indicated. (B) Venn diagram indicating the number of significant MYCN and RUVBL2 CUT&RUN peaks (targets) for 3 replicates. The targets that were identified by minimally 2 out of 3 replicates were used for further analysis (reported in panels C, E, and F). (C) Venn diagram indicating overlap between protein-coding gene targets determined with MYCN and RUVBL2 CUT&RUN. (D) Heatmaps showing peaks scores at the transcription start (TSS) ±4 kb of RUVBL2 and MYCN targets for all RUVBL2 binding sites. (E) Venn diagram showing overlap between the protein-coding RUVBL2 CUT&RUN targets and up- or downregulated genes following 72 h of CB-6644 (250 nM) in CLB-BAR cells, as indicated. (F) Enrichment for RUVBL2 CUT&RUN targets of up- and downregulated genes following different CB-6644 (250 nM) treatment durations as indicated. Odds ratios and corresponding p values calculated using Fisher’s exact test. See for detailed MYCN and RUVBL2 CUT&RUN results. CUT&RUN performed in triplicate. Results in A and D are from replicate 1. See for the results from replicates 2–3.

Article Snippet: CB-6644 , MedChemExpress , Cat# HY-114429.

Techniques: Binding Assay

Journal: iScience

Article Title: RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells

doi: 10.1016/j.isci.2026.115236

Figure Lengend Snippet: Clinical validation of the prognostic and putative therapeutic relevance of the RUVBL genes (A) Immunohistochemical staining for RUVBL1 and RUVBL2 in human NB tumor tissue sections as indicated. Normal pancreatic tissue was used as negative control for antibody specificity. Images are representative of 3 independent NB tumors and 2 independent pancreatic stained tissues. (B–E) Analysis of publicly available primary neuroblastoma data (data from Cangelosi et al. ; n = 364). (B) Correlation plots between RUVBL1 (top), RUVBL2 (bottom), and MYCN gene expression (log2 normalized counts) for MYCN amplified and MYCN wild-type tumors. Linear regression line and Pearson’s correlation coefficient indicated. (C) Boxplots comparing RUVBL1 (top) and RUVBL2 (bottom) expression between MYCN amplified and MYCN wild-type tumors. p value calculated using two-sided Wilcoxon rank-sum test. (D) Kaplan-Meier survival plots comparing overall survival between patients with high and low RUVBL1 and RUVBL2 as indicated. High/low RUVBL1/2 expression defined based on median gene expression. p value calculated using log-rank test. (E) Forest plots comparing hazard ratios ±95% confidence intervals for 4 variables as indicated. Results were obtained using a Cox proportional hazards multivariate regression analysis. (F) Time-dependent effect of CB-6644 (250 nM or 500 nM as indicated) on human NB PDX organoid growth. Organoid growth was monitored by scanning confluency at regular intervals with IncuCyte live cell analysis system. Results are mean ± SD of three technical replicates. Graph is representative of 3 biological repeats with different organoid seeding densities.

Article Snippet: CB-6644 , MedChemExpress , Cat# HY-114429.

Techniques: Biomarker Discovery, Immunohistochemical staining, Staining, Negative Control, Gene Expression, Amplification, Expressing, Cell Analysis