R723 shows selectivity and efficacy in mice. (A) Analysis of JAK2- and JAK1/JAK3-dependent STAT5 phosphorylation in primary cells. WT mice (female BALB/c) were orally dosed with vehicle, R723 50 mg/kg, or R723 100 mg/kg. Blood was collected at 1 and 3 hours after dosing and stimulated with either GM-CSF or IL-15. The percentage of pSTAT5-positive Gr-1⁺ cells with GM-CSF stimulation (left panel) and the percentage of pSTAT5-positive CD8⁺ cells with IL-15 stimulation (right panel) at each time point are shown. (B) R723 is efficacious in the hemolytic anemia mouse model. Hematocrit (left panel) and RBC count (right panel) changes were examined in mice administered PHZ on days 0 and 1 followed by oral daily administration of R723 or vehicle on days 2-7. Hematocrit and RBC counts of naive mice on day 3 were used as a baseline. (C) NOD/SCID mice injected with Ba/F3-JAK2V617F cells were administered with saline, vehicle (hydroxypropyl methylcellulose), or 50 mg/kg of R723 twice daily. Spleens and BM were harvested 13 days after cell injection. Cell counts per spleen (left panel) and percentage of GFP⁺ cells (Ba/F3-JAK2V617F) in BM and spleen cells (right panel) are shown. Data are presented as means ± SE. **P < .01; *P < .05.