tuvusertib t0129427  (Merck KGaA)

Journal: Scientific Reports

Article Title: Comparing and combining xevinapant with ATR and PARP inhibition for the radiosensitization of HPV-negative HNSCC cells

doi: 10.1038/s41598-026-38550-3

Figure Lengend Snippet: Radiation induced G2 arrest. Exponentially growing cells were treated with increasing concentrations of tuvusertib and after 2 h irradiated as indicated. At 12 h after irradiation the cells were fixed, and the cell cycle distribution assessed by DAPI staining and flow cytometry. Results are based on 3 individual experiments per cell line. Graphs display mean and standard deviation.

Article Snippet: IAP inhibition was performed using 1 μM xevinapant (MedChemExpress) and ATR inhibition was performed using 30 nM tuvusertib (MedChemExpress) unless indicated otherwise.

Techniques: Irradiation, Staining, Flow Cytometry, Standard Deviation

Journal: Scientific Reports

Article Title: Comparing and combining xevinapant with ATR and PARP inhibition for the radiosensitization of HPV-negative HNSCC cells

doi: 10.1038/s41598-026-38550-3

Figure Lengend Snippet: Cell proliferation. Cells were seeded and after 3 h treated with substances as indicated. Five days later the respective numbers of cells were assessed. ( A ) Treatment with xevinapant and tuvusertib, ( B ) treatment with xevinapant and olaparib, ( C ) treatment with xevinapant and cisplatin and (D) treatment with tuvusertib and olaparib. Graphs ( A ) and ( B ) share identical DMSO and xevinapant values because the results were generated in combined experiments. Data are presented as normalized to the mean of the respective DMSO controls. Significant differences to DMSO-treated samples are indicated with *, ** and *** indicating p < 0.05, p < 0.01 and p < 0.001, respectively (paired, two-tailed Student’s t-test). Dotted lines indicate the number of cells seeded (normalized). Results are based on at least 3 individual experiments per cell line. Graphs display mean and standard deviation.

Article Snippet: IAP inhibition was performed using 1 μM xevinapant (MedChemExpress) and ATR inhibition was performed using 30 nM tuvusertib (MedChemExpress) unless indicated otherwise.

Techniques: Generated, Two Tailed Test, Standard Deviation

Journal: Scientific Reports

Article Title: Comparing and combining xevinapant with ATR and PARP inhibition for the radiosensitization of HPV-negative HNSCC cells

doi: 10.1038/s41598-026-38550-3

Figure Lengend Snippet: Colony formation. Cells were seeded in defined low numbers and after 3 h treated with substances as indicated for 26 h, except for xevinapant with an incubation time of 1 week. Cultures were incubated until formation of colonies. ( A ) Treatment with xevinapant and tuvusertib, ( B ) treatment with xevinapant and olaparib, ( C ) treatment with xevinapant and cisplatin and ( D ) treatment with tuvusertib and olaparib. Graphs ( A ) and ( B ) share identical DMSO and xevinapant values because the results were generated in combined experiments. Significant differences to the respective solvent controls are indicated with *, ** and *** indicating p < 0.05, p < 0.01 and p < 0.001, respectively (paired, two-tailed Student’s t-test). Results are based on at least 4 individual experiments per cell line. Graphs display mean and standard deviation.

Article Snippet: IAP inhibition was performed using 1 μM xevinapant (MedChemExpress) and ATR inhibition was performed using 30 nM tuvusertib (MedChemExpress) unless indicated otherwise.

Techniques: Incubation, Generated, Solvent, Two Tailed Test, Standard Deviation

Journal: Scientific Reports

Article Title: Comparing and combining xevinapant with ATR and PARP inhibition for the radiosensitization of HPV-negative HNSCC cells

doi: 10.1038/s41598-026-38550-3

Figure Lengend Snippet: Radiosensitization. Cells were seeded in defined low numbers and after 3 h treated with substances as indicated for 26 h, except for xevinapant with an incubation time of 1 week. Cultures were incubated until formation of colonies. Graphs represent the normalized dose response curves from the same experiments as shown in Fig. . ( A ) Treatment with xevinapant and tuvusertib, ( B ) treatment with xevinapant and olaparib, ( C ) treatment with xevinapant and cisplatin and ( D ) treatment with tuvusertib and olaparib. Graphs ( A ) and ( B ) share identical DMSO and xevinapant values because the results were generated in combined experiments. Significant differences to the respective solvent controls are indicated with *, ** and *** indicating p < 0.05, p < 0.01 and p < 0.001, respectively (paired, two-tailed Student’s t-test). Results are based on at least 4 individual experiments per cell line. Dose–response curves display mean and standard deviation.

Article Snippet: IAP inhibition was performed using 1 μM xevinapant (MedChemExpress) and ATR inhibition was performed using 30 nM tuvusertib (MedChemExpress) unless indicated otherwise.

Techniques: Incubation, Generated, Solvent, Two Tailed Test, Standard Deviation

Journal: bioRxiv

Article Title: ATR inhibitors synergize with mitomycin C to enhance cytotoxicity in patient-derived non-muscle invasive bladder cancer organoids

doi: 10.1101/2025.08.29.673024

Figure Lengend Snippet: ( A , B ) BTOR58 organoids were treated for 2h with 0,5 μM gemcitabine (GEM) ( A ) or 0,5 μM epirubicin (EPI) ( B ) alone or in combination with 0,4 μM berzosertib follow-up treatment for 72h. Weekly images were taken for 6 weeks after treatment and representative images at t=1, 3, and 6 weeks are shown. Cell viability assays at t=6 weeks are shown in ( C , D ). ( E , F ) UBTOR8 organoids were treated for 2h with 4 MMC, alone or in combination with 3,2 μM ceralasertib ( E ) or 25 nM tuvusertib ( F ) follow-up treatment for 72h. Representative images at t=1, 3, and 6 weeks after treatment are presented. Cell viability assays at t=6 weeks are shown in ( G , H ). Bar graphs represent mean with SD (n=3).

Article Snippet: Next, PDOs were washed three times with PBS, before BM2+ culture medium was added, and 20h later berzosertib, ceralasertib (TargetMol #T3338), or tuvusertib (TargetMol #T10406) was added for 3 days.

Techniques:

Journal: Cancer Research

Article Title: Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors

doi: 10.1158/0008-5472.CAN-23-3603

Figure Lengend Snippet: PARPi and ATRi have synergistic cytotoxic effects in models of DSRCT with high PARP1 expression. A and B, PARP1 expression ( A ) and PARylation levels ( B ) as assessed by IHC in a cohort of 16 DSRCT samples, compared with those of the JN1 and R cell lines (PARP1 and PAR expression levels are shown as H-scores). Representative cases (PARP1-high vs. PARP1-low tumors; PAR-high vs. PAR-low tumors) are shown to the right, compared with JN1 and R cells. C and D, Surface plots of Bliss independence scores calculated for the talazoparib–M4344 combination in JN1 ( C ) and R ( D ) cell lines at 7 days. E, The GR_13-PDX-O model was established from the primary peritoneal tumor of a patient with DSRCT, with confirmation of EWSR1::WT1 fusion by FISH and WT1-Cter IHC (Supplementary Fig. S8). F, Surface plot of Bliss independence scores calculated for the talazoparib–M4344 combination in the GR_13 PDX-O at 7 days. Mean ± SD; n = 3. Surface plots: the x -axis and y -axis values indicate drug concentrations, and the z -axis values indicate the associated synergy score; score < −10, antagonistic interaction; score = 0, absence of interaction; score > 10, synergistic interaction. G, Schematic illustration of an in vivo therapeutic experiment performed to evaluate the antitumor effect of PARPi talazoparib and ATRi M1774 in NSG mice engrafted with JN1 xenografts. H, Therapeutic responses to drug treatment in mice harboring JN1 xenografts. Mean tumor volume ± SD; two-way ANOVA and post hoc Dunnett test. I, Tumor volume at the time of mice sacrifice. Mean ± SD; one-way ANOVA and post hoc Šídák test. *, P < 0.01; ns, not significant. Tala, talazoparib.

Article Snippet: The ATRi tuvusertib (M1774) was provided by Merck.

Techniques: Expressing, In Vivo

Journal: MedComm

Article Title: Targeting the DNA damage response in cancer

doi: 10.1002/mco2.788

Figure Lengend Snippet: Ataxia‐telangiectasia‐and‐Rad3‐related protein (ATR) inhibitors in clinical development.

Article Snippet: Tuvusertib (M1774) is a small molecule, ATR inhibitor, developed by EMD Serono, active at nM concentrations.

Techniques: Expressing