In vivo pharmacokinetics, pharmacodynamics, and efficacy studies of ruxolitinib-based PROTAC compound 7. (A) Plasma concentration of compound (Cmpd) 7 in a mouse injected intraperitoneally with a single dose. (B) Phosphoflow analysis of Cmpd 7’s effect on the JAK-STAT signaling pathway in vivo. (C) Degradation of JAK family kinases and GSPT1 by Cmpd 7 in vivo. (D-E) Cmpd 7, but not ruxolitinib, slowed leukemia growth in a patient-derived xenograft. (D) Bioluminescence imaging at day 32 after transplantation, 2 days before the end of the study. (E) Leukemia burden during the study. Cmpd 7 reduced spleen size (F) and tumor burden (G) in a patient-derived xenograft model. (H) Weight of NSG mice dosed with compounds and vehicle in an in vivo efficacy study. Xenograft of SJBALL047370 (CRLF2r/KRAS G12D/JAK2 wild type) was used in this in vivo study. **P < .01, ***P < .001, ****P < .0001.