Structural activity relationship of CARM1 degraders. (A) Chemical structures of CARM1 degraders, 2a-2e bearing a flexible alkyl linker, 3a-3e bearing a rigid linker that contains the combination of piperidine and piperazine rings. (B) and (C) MCF7 cells were treated with the compounds at the indicated concentrations for 24 h. Cell lysates were collected and the CARM1 levels were detected by western blots. The results are representative of three independent experiments. (D) MCF7 cells were treated with DMSO and 0.5 μM of 3b, 3c, 3d, and 3e for 24 h.