Figure 2

Time and dose optimization of JNJ-26366821 administration. (A) Optimization of JNJ-26366821 dose to improve survival of lethally irradiated CD2F1 mice when administered SC 4 h after 9.75 Gy TBI (n = 24/group). Survival curves shown here are saline as the vehicle (●) and JNJ-26366821 at doses of 0.1 mg/kg (■), 0.3 mg/kg (▲), 1.0 mg/kg (▼), and 3.0 mg/kg (♦), Percent survival on day 30 post-TBI is shown at the end of each curve. Kaplan–Meier survival curves were plotted using GraphPad software; n = 24 mice per group and trend in survival is compared between vehicle and drug-treated groups (Log-rank test p = 0.0001–0.2515). (B) Optimization of JNJ-26366821 dose to improve survival of lethally irradiated CD2F1 mice when administered SC 24 h after 9.35 Gy TBI (n = 24/group). Survival curves shown here are saline as the vehicle (○) and JNJ-26366821 doses 0.1 mg/kg (●), 0.3 mg/kg (■), 1.0 mg/kg (Δ), 2.0 mg/kg (▼) and 3.0 mg/kg (□). Percent survival on day 30 post-TBI is shown at the end of each curve. Kaplan–Meier survival curves were plotted using GraphPad software; n = 24 mice per group and trend in survival is compared between vehicle and drug-treated groups. (C) Effect of TPOm administration SC at 4, 8 and 12 h post-TBI (9.75 Gy, n = 24/group) in CD2F1 mice. Survival curves shown here are saline as the vehicle at 4 h (○), 8 h (Δ), 12 h (□) and JNJ-26366821 at 4 h (●), 8 h (▲) and 12 h (■) post-TBI. Percent survival values on day 30 post-TBI are shown at the end of each curve. Kaplan–Meier survival curves were plotted using GraphPad software; n = 20 mice per group and trend in survival is compared between vehicle and drug-treated groups (Log-rank test p = 0.0001–0.0019). Figures were plotted using GraphPad Prism 9 software V9.0.2; www.graphpad.com.