PROTAC YX-2-107 metabolic stability and its biological activity in a mouse xenograft of Ph⁺ ALL. (A) Half-life of YX-2-107, palbociclib, and E3 ligase–recruiting molecules incubated in mouse liver microsomes. (B) Time course of plasma concentration of YX-2-107 injected intraperitoneally at 10 mg/kg into C57BL/6j mice and its PK property (left). Cell cycle analysis by propidium iodide staining (C) and immunoblot for phospho-RB, FOXM1, CDK4, and CDK6 (D), with densitometry of CDK4 and CDK6 expression (E) of bone marrow leukemic cells (>90% CD19⁺CD10⁺ by flow cytometry), from NSG mice injected with Ph⁺ ALL cells and treated (3 mice/group) with palbociclib or YX-2-107 at 150 mg/kg per day for 3 consecutive days when peripheral blood leukemic cells were 50%. Bone marrow leukemic cells were purified 24 hours after the cessation of drug treatment. N.S., not significant.