c myc inhibitor  (MedChemExpress)

Journal: bioRxiv

Article Title: ATM functions as a rheostat of metabolic stress in small-cell lung cancer

doi: 10.64898/2026.03.13.711672

Figure Lengend Snippet: (A) ATAC-seq track showing chromatin accessibility at the ATF4 gene locus in H82 SCLC cells. MYC ChIP-seq tracks illustrating MYC binding at the ATF4 promoter region across 3 SCLC cell lines: NCI-H128, NCI-H2171, and SW1271. Gene orientation and structure are displayed using the UCSC Genes track (University of California, Santa Cruz, genome browser), with ATF4 transcribed from left to right on chromosome 22. Blue bars indicate annotated exons. Black bars beneath the ATAC-seq track indicate significant peak calls, marking regions of accessible chromatin, while black bars beneath the ChIP-seq tracks denote significant MYC binding peaks. (B) Boxplots showing MYC target gene signature scores in SCLC cells treated with ATMi AZD0156 (red) compared to DMSO controls (gray) across 3 SCLC cell lines: DMS114, H196, and H446. P -values were calculated using a 2-sample t -test and were adjusted using the BH method ( P -adj: DMS114 - 0.00317, H196 - 0.0152, and H446 - 0.0169). (C) Western blot of H446 and H196 showing expression of MYC after ATM inhibition +/- MG132 (inhibitor of proteosome-mediated degradation). Vinculin is visualized as a loading control. (D-E) Confocal image of SCLC models (H446, H196) +/- ATMi showing immunofluorescence for MYC. DAPI was stained to visualize nuclei. Scalebar = 25 µm. Mean intensity of MYC in the nucleus was quantified with or without ATMi. P -value was calculated by Student’s t -test. (F-G) Western blot of H446 cells stably expressing MYC-shRNA (F) or in H446 and H196 stably overexpressing MYC (G) compared to vector control, +/- ATMi (AZD0156) probed for MYC, ATF4, and vinculin. (H) Heatmap showing cell viability (CTG) of H446 and H196 treated with or without ATMi (AZD0156) and depleted of 1 amino acid at a time. (I) Bar plot showing cell viability (measured by CTG) in complete and depleted/minimal media +/- ATMi and/or stably overexpressing MYC. P values were calculated using Student’s t -test. (J) Functional enrichment analysis of top-ranked genes identified from the CRISPR screen. Genes selected from the lower end of the sigmoid-ranked essentiality curve were analyzed for pathway enrichment. Lollipop plots display the top enriched biological processes at T1 and T2, with statistical significance indicated by -log₁₀(nominal P -value) (color scale) and gene ratio (dot size). Significant pathways are indicated in bold.

Article Snippet: Other inhibitors used were AKT inhibitor MK-2206 (Medchemexpress), mTORC1 inhibitor rapamycin (Thermo Scientific), apoptosis inhibitor ZVAD (Selleckchem, 187389-52-2), apoptosis inducer (PKC inhibitor) Staurosporin (Selleckchem, NC1828540), ferroptosis inhibitor ferrostatin (Cayman Chemical), xCT inhibitor erastin (Selleckchem, 50-136-4551), GSH peroxidase 4 (GPX4) inhibitor RSL3, and AIFM2/FSP1 inhibitor iFSP1 (Fisher Scientific), MG132 (Cayman Chemical, 133407-82-6), and MYC inhibitor (MYCi975, Selleck Chem, S8906).

Techniques: ChIP-sequencing, Binding Assay, Western Blot, Expressing, Inhibition, Control, Immunofluorescence, Staining, Stable Transfection, shRNA, Plasmid Preparation, Functional Assay, CRISPR

Journal: bioRxiv

Article Title: ATM functions as a rheostat of metabolic stress in small-cell lung cancer

doi: 10.64898/2026.03.13.711672

Figure Lengend Snippet: (A) Boxplot representing SLC7A11 mRNA expression from the Jiang et al. microarray dataset of SCLC compared to normal lung tissue (TPM-normalized RNA-seq, Wilcoxon rank-sum test, ** P < 0.01). (B-C) Boxplot representing SLC7A11 (B) and TFRC (C) expression in SCLC clinical samples relative to normal controls in the GSE43346 microarray dataset using globally normalized counts (*** P < 0.001). (D) Nine-square plot comparing gene-level beta scores at timepoint T1 versus T0. The x -axis represents gene enrichment or depletion in the control condition, while the y -axis shows the same for the treatment condition. Genes in the top-center quadrant (deep-red, n = 35) exhibit strong enrichment under treatment but not control, whereas genes in the bottom-center quadrant (blue, n = 160) show strong depletion under treatment but not control. Genes in gray represent non-significant hits. Top candidate genes are labeled, including positive hits such as ZNF345, ACS1 and VDAC3, and negative hits such as ATG16L2, EIF4, and ZNF66 . (E) Functional enrichment analysis of top-ranked genes identified from the CRISPR screen. Genes selected from the upper end (n=35 genes) of the sigmoid-ranked essentiality curve were analyzed for pathway enrichment. Lollipop plot displays the top depleted biological processes at T1, with statistical significance indicated by -log₁₀( P -value) (color scale) and gene ratio (dot size). Enriched terms reflect biological processes preferentially required under ATM inhibition (AZD0156). (F) Western blot of top ferroptosis markers SLC7A11, TFRC, and GPX4 in whole-cell lysates from H446 and H196 +/- ATMi. Vinculin was visualized as a loading control. (G) Boxplots showing ferroptosis gene signature scores in SCLC cells treated with ATMi AZD0156 (red) compared to DMSO controls (gray) across 3 SCLC cell lines: DMS114, H196, and H446. P -values were calculated using a 2-sample t -test and were adjusted using the BH method ( P -adj: DMS114 - 0.000199, H196 - 0.00217, and H446 - 0.0149). (H) Bar plot representing relative MDA content in whole-cell lysates of H446 and H196 treated with ATMi (AZD0156). (I) Bar plot representing relative lipid peroxidation at 24 h measured by BODIPY/C11 positive staining in FACS +/- ATMi (AZD0156) in SCLC models. Ferroptosis inducers (RSL3, iFSP1, erastin) or ferroptosis inhibitors (Fer-1) were used alone or in combination with AZD0156. (J) Lipid peroxidation measurement by BODIPY/C11 in H446 and H196 treated with ATMi (AZD0156) with or without stable overexpression of MYC in complete media. Data represent mean ± SEM of n = 3 biological replicates. Statistical significance was determined by 1-way Student’s t -test (* P < 0.05; ** P < 0.01; *** P < 0.001, *** * P < 0.0001). (K) Graph depicts tumor volume of mice over time treated with vehicle or ATMi (AZD0156), with tumor generated subcutaneously from LX33. 0 mg/kg AZD0156 was administered 5/7 days as an intraperitoneal injection. Data are represented as mean ± SEM ( n = 6 per group). (L) Representative image of LX33 tumor sizes from (K) . (M) IHC images of LX33 tumors +/- AZD0156 probed for expression of 4-HNE, a marker of lipid peroxidation.

Article Snippet: Other inhibitors used were AKT inhibitor MK-2206 (Medchemexpress), mTORC1 inhibitor rapamycin (Thermo Scientific), apoptosis inhibitor ZVAD (Selleckchem, 187389-52-2), apoptosis inducer (PKC inhibitor) Staurosporin (Selleckchem, NC1828540), ferroptosis inhibitor ferrostatin (Cayman Chemical), xCT inhibitor erastin (Selleckchem, 50-136-4551), GSH peroxidase 4 (GPX4) inhibitor RSL3, and AIFM2/FSP1 inhibitor iFSP1 (Fisher Scientific), MG132 (Cayman Chemical, 133407-82-6), and MYC inhibitor (MYCi975, Selleck Chem, S8906).

Techniques: Expressing, Microarray, RNA Sequencing, Control, Labeling, Functional Assay, CRISPR, Inhibition, Western Blot, Staining, Over Expression, Generated, Injection, Marker

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Design of anti-transcription γPNA and combination treatments to target the c-Myc oncogene (A) Schematic representation of gamma peptide nucleic (γPNA)-mediated inhibition of human c-Myc transcription and target site (NCBI database RefSeq: NG_007161.2 ). (B) Design of γPNA conjugated with nuclear localization signal (NLS) to target the indicated sites. ScR-γPNA2 is the scramble control. (C) Graphic representation of combination treatments with anti-transcription, γPNA1. The combination treatments include histone deacetylase inhibitors (HDACis), MYC/MAX inhibitors, small interfering RNA (siRNA), and small molecules targeting other pathways. (D) Polymerase chain reaction (PCR)-based amplicon assay to confirm binding of γPNA1 to the target site in U2932 cells. Amplicon assay after treatment of γPNA1 and ScR-γPNA2 with HDACi. (E) The graph represents quantification of γPNA1 and ScR-γPNA2 amplicon in combination with HDACi. (F) The graph represents the quantification of amplicon assay from class I HDACi with γPNA1. Results are presented as mean ± SEM. One-way ANOVA was used to determine the statistically significant difference between groups.

Article Snippet: Cells were cotreated with 1:2 dilutions of MYC/MAX inhibitors (Myci975 [Selleckchem, #S8906]), EN4 (MedChemExpress, #HY-134761), 10058-F4 (MedChemExpress, #HY-12702), SAJM589 (MedChemExpress, #HY-122683), and γPNA1 and ScR-γPNA2 at 8 μM for 72 h. Cells were cotreated with 1:10 dilutions of small molecule inhibitors (JQ1 [MedChemExpress, #HY-13030]), sapanisertid (MedChemExpress, #HY-13328), and γPNA1 and ScR-γPNA2 at 8 μM for 72 h. MDA-MB 231 cells were cotreated with dinaciclid (MedChemExpress, #HY-10492) and γPNA1 and ScR-γPNA2 at 8 μM for 72 h. MDA-MB-231 and HeLa cells were cotreated with c-Myc siRNA (50 nM) and γPNA1 and ScR-γPNA2 for 48 h. At 0 μM concentration, cells were treated only with PBS and not treated with MYC/MAX inhibitors, HDAC inhibitors, small molecule inhibitors, or γPNA1.

Techniques: Inhibition, Control, Histone Deacetylase Assay, Small Interfering RNA, Polymerase Chain Reaction, Amplification, Binding Assay

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: MYC/MAX inhibitors in combination with anti-transcription γPNA1 Cell viability of (A) U2932 and (B) Raji cells treated with increasing doses of MYC/MAX inhibitors (Myci975, EN4, 10058-F4, and sAJM589) alone and in combination with γPNA1 and ScR-γPNA2 (8 μM) for 72 h. Results are presented as mean ± SEM. The IC 50 (95% CI) values of MYC/MAX inhibitors alone and combination treatment of MYC/MAX with γPNA1 in (C) U2932 and (D) Raji cells. (E) Cell viability of γPNA1-treated U2932 and Raji cells at 8 μM concentration. Western blot analysis representing the change in c-MYC protein 72 h after treatment with γPNA1 and ScR-γPNA2 in combination with (F) Myci975, (G) EN4, (H) 10058-F4, and (I) sAJM589. ∗∗(F–I) Cyclophilin B was used as an endogenous control, and the same blots are presented in A–S7D. c-MYC, EZH2, and cyclophilin B were probed from the same blot. Results are presented as mean ± SEM, p value for one-way ANOVA.

Article Snippet: Cells were cotreated with 1:2 dilutions of MYC/MAX inhibitors (Myci975 [Selleckchem, #S8906]), EN4 (MedChemExpress, #HY-134761), 10058-F4 (MedChemExpress, #HY-12702), SAJM589 (MedChemExpress, #HY-122683), and γPNA1 and ScR-γPNA2 at 8 μM for 72 h. Cells were cotreated with 1:10 dilutions of small molecule inhibitors (JQ1 [MedChemExpress, #HY-13030]), sapanisertid (MedChemExpress, #HY-13328), and γPNA1 and ScR-γPNA2 at 8 μM for 72 h. MDA-MB 231 cells were cotreated with dinaciclid (MedChemExpress, #HY-10492) and γPNA1 and ScR-γPNA2 at 8 μM for 72 h. MDA-MB-231 and HeLa cells were cotreated with c-Myc siRNA (50 nM) and γPNA1 and ScR-γPNA2 for 48 h. At 0 μM concentration, cells were treated only with PBS and not treated with MYC/MAX inhibitors, HDAC inhibitors, small molecule inhibitors, or γPNA1.

Techniques: Concentration Assay, Western Blot, Control