BTK degrader DD-03-171 shows on-target efficacy against MCL cells in vitro and in vivo. (A) Immunoblots from Mino cells treated as indicated for 18 hours; all bands for IKZF1 are specific. (B) Quantitative proteomics showing relative abundance of proteins in Mino cells treated with 200 nM DD-03-171 or DD-04-118 for 4 hours. (C) Mino cells were treated with the indicated compounds and concentrations for 3 days. Antiproliferative effects of compounds were assessed using the CellTiter-Glo assay (Promega), and ED₅₀ values were determined using a GraphPad Prism nonlinear regression curve fit. (D) Immunoblot from mouse-depleted spleen samples of NSG mice engrafted with DFBL-96069 and treated for 3 days with the indicated compounds: vehicle (intraperitoneal [IP], twice daily), DD-03-171 (IP, daily, 50 mg/kg), lenalidomide (IP, daily, 50 mg/kg), ibrutinib (oral, daily, 30 mg/kg). All bands for IKZF1 are specific; each lane represents an individual tumor from different mice (3 mice per treatment cohort). (E) Tumor burden in mice treated for 2 weeks. Four to six hours after the last dose, peripheral blood was quantified for disease burden via flow cytometry. *P < .05. (F) Kaplan-Meier survival curve of mice treated as in panels D and E.