epigenetic modifications  (Epigenomics ag)

Journal: bioRxiv

Article Title: Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancer

doi: 10.64898/2026.04.16.719008

Figure Lengend Snippet: High-throughput drug screen and MEK inhibitor sensitivity in MRTX1719-resistant NSCLC cells. (A) Composition of the compound library used for drug screen, including SGC epigenetic compounds, FDA-approved oncology drugs, and TargetMol epigenetic inhibitors. (B) IC50 values of MRTX1719 and anisomycin in DMSO and MRTXR cells. Anisomycin was included as a nonselective control in the drug screen. (C) Dose-response curves of DMSO and MRTXR cells treated with the MEK inhibitor selumetinib. Data are presented as mean ± SD. (D) Synergy heatmaps of MRTX1719 and selumetinib in DMSO and MRTXR cells. Synergy mean scores were calculated using the Bliss model with the SynergyFinder+ tool.

Article Snippet: The screening library comprised 619 compounds, including SGC epigenetic compounds, TargetMol epigenetic inhibitors, and FDA-approved oncology drugs ( ).

Techniques: High Throughput Screening Assay, Drug discovery, Control

Journal: bioRxiv

Article Title: Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancer

doi: 10.64898/2026.04.16.719008

Figure Lengend Snippet: High-throughput drug screen and MEK inhibitor sensitivity in MRTX1719-resistant NSCLC cells. (A) Composition of the compound library used for drug screen, including SGC epigenetic compounds, FDA-approved oncology drugs, and TargetMol epigenetic inhibitors. (B) IC50 values of MRTX1719 and anisomycin in DMSO and MRTXR cells. Anisomycin was included as a nonselective control in the drug screen. (C) Dose-response curves of DMSO and MRTXR cells treated with the MEK inhibitor selumetinib. Data are presented as mean ± SD. (D) Synergy heatmaps of MRTX1719 and selumetinib in DMSO and MRTXR cells. Synergy mean scores were calculated using the Bliss model with the SynergyFinder+ tool.

Article Snippet: A high-throughput drug screen was performed using a compound library consisting of 619 compounds, including 59 SGC epigenetic compounds, 380 TargetMol epigenetic inhibitors and 180 FDA-approved oncology drugs.

Techniques: High Throughput Screening Assay, Drug discovery, Control

Journal: bioRxiv

Article Title: Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancer

doi: 10.64898/2026.04.16.719008

Figure Lengend Snippet: High-throughput drug screen and MEK inhibitor sensitivity in MRTX1719-resistant NSCLC cells. (A) Composition of the compound library used for drug screen, including SGC epigenetic compounds, FDA-approved oncology drugs, and TargetMol epigenetic inhibitors. (B) IC50 values of MRTX1719 and anisomycin in DMSO and MRTXR cells. Anisomycin was included as a nonselective control in the drug screen. (C) Dose-response curves of DMSO and MRTXR cells treated with the MEK inhibitor selumetinib. Data are presented as mean ± SD. (D) Synergy heatmaps of MRTX1719 and selumetinib in DMSO and MRTXR cells. Synergy mean scores were calculated using the Bliss model with the SynergyFinder+ tool.

Article Snippet: A high-throughput drug screen was performed using a compound library consisting of 619 compounds, including 59 SGC epigenetic compounds, 380 TargetMol epigenetic inhibitors and 180 FDA-approved oncology drugs.

Techniques: High Throughput Screening Assay, Drug discovery, Control

Journal: Cell Death & Disease

Article Title: Identification of targetable epigenetic vulnerabilities for uveal melanoma

doi: 10.1038/s41419-025-08295-4

Figure Lengend Snippet: A Mean viability of the three UM cell lines following 72 h treatment with 932 epigenetic modulators at a concentration of 1 μM ( n = 2) relative to the negative control (0.1% DMSO treatment). Hit cut-offs (dashed lines) were determined as the mean percentage viability of the negative controls in each cell line minus three standard deviations. Yellow dashed line is the hit cut-off for MP41 cells (65.8% viability), purple dashed line is the hit cut-off for MP46 cells (74.0% viability), and the green dashed line is the hit cut-off for MP38 cells (58.9% viability). For full list of compounds and average UM cell viabilities, see Supplementary Data . B Radar plot showing the mean difference in percent of cell viability of UM cells caused by 72 h 1 μM treatment with 932 compounds, relative to the DMSO control. Negative values, shown in gray, indicate ineffective compounds leading to greater cell viability than the negative control. The positive values, shown in color, indicate compounds that induced cell death, with higher peaks indicating greater cell death. Compounds are grouped by drug mechanism of action. C Pie charts of the molecular activities of all screened compounds ( n = 932) (left) and the hits identified ( n = 24) (right). D Concentration-response experiments for the 24 hit compounds (10 concentrations, n = 4 per concentration per cell line). Center values represent mean viability, error bars represent standard error of mean (SEM). E Log IC 50 (M) values of the top hit compounds for each cell line. Error bars represent 95% confidence interval. F Log IC 50 (M) of BAP1 mutant cell lines (MP46 and MP38) plotted against the log IC 50 (M) of the BAP1 wildtype cell line (MP41) for each drug treatment.

Article Snippet: Given the global epigenetic changes elicited by BAP1 loss, we performed a comprehensive epigenetic compound screen on UM cells, using a well-characterized drug library consisting of 932 cell-permeable, small-molecule modulators (TargetMol, L1200, July 2022; Supplementary Data ).

Techniques: Concentration Assay, Negative Control, Control, Mutagenesis