Validation of image-based degradation studies. a, Structures of rationally redesigned ALK PROTACs to minimize off-target ZF degradation. b, Degradation of validated and pomalidomide-sensitive ZF degrons inside cells by redesigned ALK PROTACs in a dosing range of 4.3 nM to 6 μM. Data are the mean of three independent replicates. c,d, Global proteomic analysis of KELLY cells treated with 100 nM of MS4078 (c) or dALK-10 (d), respectively. e, Determination of EC50 values (nM) of SU-DH-L1 cells upon treatment with redesigned ALK PROTACs. Error bars represent mean ± standard deviation from three biological replicates. FC, fold change.