ibrutinib  (MedChemExpress)

Journal: iScience

Article Title: Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases

doi: 10.1016/j.isci.2026.115339

Figure Lengend Snippet: In vitro experimental validation of the complement-type doublets and triplets that were predicted via SYNERGIE for CRC (A) The top 18 predicted complement-type drug combinations for CRC using the SYNERGIE-ET. The horizontal axis represents the drug combinations, whereas the vertical axis corresponds to the five types of prediction scores (see ). Blue and green indicate the prediction scores for drug A and drug B, respectively, with the color intensity reflecting the magnitude of the scores. Details can be found in . (B–I) Comparison of the survival ratios of CRC cells among Asp, an antineoplastic drug, and their combination. Gray represents single drugs (singlets), and blue represents the combination (doublet). Data are presented as mean values from independent experiments. Standard deviation values are provided in the . (J–O) Comparison of the survival ratios of CRC cells among PB, an antineoplastic drug, and their combination. These panels follow the same format as (B–I). (P) Heatmap of the dose-response synergy scores of Asp doublets. The vertical axis represents the doses of Asp, and the horizontal axis shows drugs predicted to be Asp partners. The color scale reflects the IA scores, with positive values indicating synergistic effects and negative values indicating nonsynergistic effects. Each box is annotated with the corresponding IA score. Data are presented as mean values from independent experiments. Standard deviation values are provided in the . (Q) Comparison of the dose-response survival ratios between Oxa, a first-line drug for CRC, alone (singlet) and the Oxa-Asp doublet. In the Oxa-Asp doublet, the dose of Asp was fixed at 1 mM while the dose of Oxa was varied. The horizontal and vertical axes represent the doses of Oxa (μM) and the mean survival ratios of CRC cells, respectively. Error bars represent standard deviations (SD). The gray and blue points correspond to Oxa and the Oxa-Asp combination, respectively. The color bar reflects the IA scores for each drug combination, with values indicating the IA scores. (R) Comparison of CRC cell survival ratios among singlets, doublets, and the triplet combination: Oxa, Asp, and Ibru. The horizontal axis represents the drugs, and the vertical axis represents the mean survival ratios. Error bars indicate SD. The color bar reflects the IA scores for each drug combination, with values indicating the IA scores. Disease abbreviations: CRC, colorectal cancer. Drug abbreviations: Asp, aspirin; Chl, chlorotrianisene; Ced, cediranib; Das, dasatinib; Ibru, ibrutinib; Inf, infigratinib; Luc, lucitanib; Mir, mirdametinib; Oxa, oxaliplatin; PB, sodium phenylbutyrate; Pim, pimasertib; Pon, ponatinib; Sar, saracatinib; Tac, tacedinaline; Tan, tanespimycin; and Van, vandetanib.

Article Snippet: Lucitanib and ibrutinib were purchased from MedChemexpress (South Brunswick Township, NJ, USA).

Techniques: In Vitro, Biomarker Discovery, Comparison, Standard Deviation

Journal: iScience

Article Title: Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases

doi: 10.1016/j.isci.2026.115339

Figure Lengend Snippet: Omics analyses of the synergistic effects of the predicted Ibru-Asp doublet combined with Oxa, a first-line drug in CRC (A–C) Drug-disease associations based on the transcriptome pattern comparisons (A) between Ibru and CRC, (B) between Asp and CRC, and (C) between Oxa and CRC. The horizontal axis represents the transcriptome signature score after drug treatment in HT29 cells, and the vertical axis represents the CRC transcriptome signature scores. The color intensity corresponds to the significance of the gene expression ratios in CRC. Gene expression changes were assessed using linear models with empirical Bayes moderation, with p values adjusted using the Benjamini–Hochberg method. Exact p values are provided in . The pink line represents the regression line, and the light pink area around the line represents the 95% confidence interval (CI). (D–F) Drug-drug associations based on the transcriptome pattern comparisons (D) between Ibru and Asp, (E) between Ibru and Oxa, and (F) between Asp and Oxa. Horizontal and vertical axes represent the transcriptome signature scores after each drug treatment in HT29 cells. The color intensity corresponds to the significance of the gene expression ratios in CRC. Gene expression changes were assessed using linear models with empirical Bayes moderation, with p values adjusted using the Benjamini–Hochberg method. Exact p values are provided in . The pink line represents the regression line, and the light pink area around the line represents the 95% confidence interval (CI). This panel follows the same format as (A–C). (G and H) Venn diagrams showing the distribution of (G) upregulated and (H) downregulated DEGs in CRC and the Oxa–Ibru–Asp triplet. (I and J) Heatmaps of all pathways significantly enriched for (I) upregulated and (J) downregulated DEGs in singlets, doublet, and triplet. The horizontal axis represents pathways, and the vertical axis represents drug combinations. The heatmap’s color intensity represents − log ⁡ ( p - value ) , with pathway categories shown in the color bar above the heatmap. The asterisks for each square reflect statistical significance (∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001). Enrichment analysis was performed by Fisher’s exact test. Corrections for multiple testing were applied, adjusting significance values based on the number of pathway terms. Exact p values are provided in and . Further details can be found in . (K and L) Synergistic mechanisms of the Oxa-Ibru-Asp triplet. (K) On the left, the diagram shows the regulatory flow from BCR signaling to calcium signaling, coordinated upstream by Ibru and downstream by the triplet. On the right, the diagram shows the regulatory flow from AMPK signaling to PIP3K/Akt/mTOR signaling, coordinated upstream by the triplet and downstream by Oxa. (L) Synergistic mechanism of the Oxa–Asp doublet. The diagram illustrates the regulatory flow from DNA synthesis to protein synthesis, coordinated upstream by Asp and downstream by Oxa. Created with BioRender.com . (M and N) Enrichment frequency of pathways important for CRC treatment with significantly (M) upregulated and (N) downregulated DEGs in each drug. Gray corresponds to singlets; red or blue correspond to the doublets or triplet. (O and P) Heatmaps of enriched pathways important for CRC treatment using (O) upregulated and (P) downregulated DEGs in the singlets, doublets, and triplet. The histograms on the horizontal and vertical axes represent the enrichment frequency of the pathways. The heatmap’s color intensity represents − log ⁡ ( p value ) , with pathway categories shown in the color bar above the heatmap. Enrichment analysis was performed by Fisher’s exact test. Corrections for multiple testing were applied, adjusting significance values based on the number of pathway terms. Exact p values are provided in and . This panel follows the same format as (I–J). Drug abbreviations: Asp, aspirin; Ibru, ibrutinib; Oxa, oxaliplatin.

Article Snippet: Lucitanib and ibrutinib were purchased from MedChemexpress (South Brunswick Township, NJ, USA).

Techniques: Gene Expression, DNA Synthesis

Journal: iScience

Article Title: Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases

doi: 10.1016/j.isci.2026.115339

Figure Lengend Snippet: In vitro experimental validation of the complement-type doublets and triplets that were predicted via SYNERGIE for CRC (A) The top 18 predicted complement-type drug combinations for CRC using the SYNERGIE-ET. The horizontal axis represents the drug combinations, whereas the vertical axis corresponds to the five types of prediction scores (see ). Blue and green indicate the prediction scores for drug A and drug B, respectively, with the color intensity reflecting the magnitude of the scores. Details can be found in . (B–I) Comparison of the survival ratios of CRC cells among Asp, an antineoplastic drug, and their combination. Gray represents single drugs (singlets), and blue represents the combination (doublet). Data are presented as mean values from independent experiments. Standard deviation values are provided in the . (J–O) Comparison of the survival ratios of CRC cells among PB, an antineoplastic drug, and their combination. These panels follow the same format as (B–I). (P) Heatmap of the dose-response synergy scores of Asp doublets. The vertical axis represents the doses of Asp, and the horizontal axis shows drugs predicted to be Asp partners. The color scale reflects the IA scores, with positive values indicating synergistic effects and negative values indicating nonsynergistic effects. Each box is annotated with the corresponding IA score. Data are presented as mean values from independent experiments. Standard deviation values are provided in the . (Q) Comparison of the dose-response survival ratios between Oxa, a first-line drug for CRC, alone (singlet) and the Oxa-Asp doublet. In the Oxa-Asp doublet, the dose of Asp was fixed at 1 mM while the dose of Oxa was varied. The horizontal and vertical axes represent the doses of Oxa (μM) and the mean survival ratios of CRC cells, respectively. Error bars represent standard deviations (SD). The gray and blue points correspond to Oxa and the Oxa-Asp combination, respectively. The color bar reflects the IA scores for each drug combination, with values indicating the IA scores. (R) Comparison of CRC cell survival ratios among singlets, doublets, and the triplet combination: Oxa, Asp, and Ibru. The horizontal axis represents the drugs, and the vertical axis represents the mean survival ratios. Error bars indicate SD. The color bar reflects the IA scores for each drug combination, with values indicating the IA scores. Disease abbreviations: CRC, colorectal cancer. Drug abbreviations: Asp, aspirin; Chl, chlorotrianisene; Ced, cediranib; Das, dasatinib; Ibru, ibrutinib; Inf, infigratinib; Luc, lucitanib; Mir, mirdametinib; Oxa, oxaliplatin; PB, sodium phenylbutyrate; Pim, pimasertib; Pon, ponatinib; Sar, saracatinib; Tac, tacedinaline; Tan, tanespimycin; and Van, vandetanib.

Article Snippet: Lucitanib , MedChemExpress , Cat# HY-18951.

Techniques: In Vitro, Biomarker Discovery, Comparison, Standard Deviation