Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models
<p>Polθ inhibitor ART899 combined with radiation causes significant tumor growth delay <i>in vivo</i> and is well tolerated. <b>A,</b> ART899 plasma concentration following oral dosage of ART899 at 50 or 150 mg/kg. Mouse plasma samples (<i>n</i> = 3 per trea...
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2025
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| Sažetak: | <p>Polθ inhibitor ART899 combined with radiation causes significant tumor growth delay <i>in vivo</i> and is well tolerated. <b>A,</b> ART899 plasma concentration following oral dosage of ART899 at 50 or 150 mg/kg. Mouse plasma samples (<i>n</i> = 3 per treatment group) were collected at 30 minutes, 1, 2, 4, 8, and 12 hours after last dose. <b>B–E,</b> HCT116 tumor-bearing mice treated with 150 mg/kg Polθ inhibitor ART899 twice daily for 12 days and/or 10 × 2 Gy (days 1–5 and 8–12). Vehicle (<i>n</i> = 9); ART899 (<i>n</i> = 10); 10 × 2 Gy + vehicle (<i>n</i> = 10); 10 × 2 Gy + ART899 (<i>n</i> = 10). <b>B,</b> Mean ± SEM relative tumor size. <i>P</i> value from mixed effect model and Dunnett post-test. Comparison of tumor size at the latest common timepoint for 10 × 2 Gy versus 10 × 2 Gy + ART899 are shown in Supplementary Fig. S6A. <b>C,</b> Individual mouse graphs. <b>D,</b> Kaplan–Meier plot for a tumor size threshold of 1,000 mm<sup>3</sup>. HR: Hazard ratio (hazard rate of IR arm / hazard rate of IR + ART899 arm); <i>P</i> value from the log-rank (Mantel-Cox) test comparing IR alone and IR + ART558. The median time to a tumor size of 1,000 mm<sup>3</sup> for the IR + ART899 arm versus the IR arm and the corresponding ratio are shown in Supplementary Fig. S6B. <b>E,</b> Average mouse weight ± SD from all treatment groups over time. Individual mouse weights are shown in Supplementary Fig. S6C.</p> |
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