tuvusertib  (TargetMol)

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

Journal: Clinical and Translational Science

Article Title: Asia‐inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler

doi: 10.1111/cts.70050

Figure Lengend Snippet: Assessment of ethnic sensitivity in exposure and safety of tuvusertib in Asian and non‐Asian patients with advanced solid tumors. (a) Dose–AUC τ,ss relationship. Relationship between tuvusertib doses and AUC τ, ss was assessed using a power model. Symbols represent individual patients (Asian patients in blue, non‐Asian patients in gray); the solid black line and the shaded gray area represent the power model‐predicted relationship and 95% prediction interval, respectively. (b) Hemoglobin reduction. Observed Hb reductions in Asians in comparison with simulated Hb levels for 4 cycles of tuvusertib treatment and various doses of interest. The dashed black line and the shaded gray area represent median and 5th–95th percentiles, respectively. The horizontal dashed black line represents Hb levels of 80 g/L. The blue symbols are for the individual Asian patients. AUC τ, ss , area under the curve; Hb, hemoglobin; q.d., once daily; w, week.

Article Snippet: Herein, we describe recent case examples of model‐informed Asia‐inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3‐related inhibitors, tuvusertib and berzosertib (oncology), the toll‐like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal–epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease).

Techniques: Comparison