Journal: Scientific Reports

Article Title: A multiparametric screen uncovers FDA-approved small molecules that potentiate the nuclear mechano-dysfunctions in ATR-defective cells

doi: 10.1038/s41598-024-80837-w

Figure Lengend Snippet: 12 selected candidates including 8 ‘worsening’ and 4 ‘reverting’ compounds.

Article Snippet: For the Confirmation some selected compounds were repurchased from Selleck Chemicals: Mometasone furoate (S1987), Dasatinib (S1021), Olaparib (AZD2281, Ku-0059436) (S1060), PF-477736 (S2904), Ruxolitinib (S1378), Y-39983 Dihydrochloride (S7935), Abemaciclib (S5716), GW3965 HCl (S2630), Everolimus (S1120).

Techniques: Migration, Protein-Protein interactions

Journal: Scientific Reports

Article Title: A multiparametric screen uncovers FDA-approved small molecules that potentiate the nuclear mechano-dysfunctions in ATR-defective cells

doi: 10.1038/s41598-024-80837-w

Figure Lengend Snippet: Analysis of the cellular mechanical properties of HeLa shATR cells treated with ‘worsening’ compounds. ( a ) Elastic modulus measurements using AFM. Cellular stiffness was measured on shATR HeLa cells treated for 24 h with DMSO or the indicated compounds: Olaparib and Mometasone were tested at 10 μM, Dasatinib at 1 μM. At least 50 cells were detected in three independent experiments. ( b ) Quantification of nuclear to cytoplasmic YAP signal ratio. shATR HeLa cells were treated with the indicated compounds at two doses for 24 h, then fixed and stained for YAP. The ratio of nuclear and cytoplasmic intensity signals was calculated after background subtraction. Data is reported as mean ± SD of three independent experiments with at least 3 technical replicates for the treated samples and at least 12 technical replicates for the controls in each experiment. **p ≤ 0.01, ****p ≤ 0.0001 by ordinary one-way ANOVA test using Bonferroni’s correction for multiple comparisons. ( c ) Immunofluorescence images showing YAP cellular distribution under the indicated conditions. Scale bar 20 μm.

Article Snippet: For the Confirmation some selected compounds were repurchased from Selleck Chemicals: Mometasone furoate (S1987), Dasatinib (S1021), Olaparib (AZD2281, Ku-0059436) (S1060), PF-477736 (S2904), Ruxolitinib (S1378), Y-39983 Dihydrochloride (S7935), Abemaciclib (S5716), GW3965 HCl (S2630), Everolimus (S1120).

Techniques: Staining, Immunofluorescence

Journal: Scientific Reports

Article Title: A multiparametric screen uncovers FDA-approved small molecules that potentiate the nuclear mechano-dysfunctions in ATR-defective cells

doi: 10.1038/s41598-024-80837-w

Figure Lengend Snippet: The ‘worsening’ compounds stimulate a cGAS-STING-mediated inflammatory ISG response in HCC1937 cells when combined with AZD6738. Heat-map graph showing the induction of a selected panel of ISG genes normalized to the DMSO condition in HCC1937 cells treated with ATRi AZD6738 3 μM for 48 h; AZD6738 was administered alone or in combination with the ‘worsening’ compounds (24 h treatment). Mometasone and Olaparib were tested at 10 μM, while PF-477736 and Dasatinib were tested at 1 μM and 0.1 μM respectively. Bar graphs show the ISG induction levels as an average of three independent biological replicates (left panel). Statistical analysis by ordinary one-way ANOVA test using Bonferroni’s correction for multiple was applied, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.

Article Snippet: For the Confirmation some selected compounds were repurchased from Selleck Chemicals: Mometasone furoate (S1987), Dasatinib (S1021), Olaparib (AZD2281, Ku-0059436) (S1060), PF-477736 (S2904), Ruxolitinib (S1378), Y-39983 Dihydrochloride (S7935), Abemaciclib (S5716), GW3965 HCl (S2630), Everolimus (S1120).

Techniques: